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Gene Information
Gene symbol: TLR4
Gene name: toll-like receptor 4
HGNC ID: 11850
Synonyms: hToll, CD284, TLR-4
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 10623794 | Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. |
| 2 | 10623794 | Both the induction of TNF-alpha and NO formation were found dependent on a functional Tlr4 whereas stimulation of macrophages by CpG DNA was Tlr4 independent. |
| 3 | 10623794 | Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. |
| 4 | 10623794 | Both the induction of TNF-alpha and NO formation were found dependent on a functional Tlr4 whereas stimulation of macrophages by CpG DNA was Tlr4 independent. |
| 5 | 11777948 | Previous studies have shown that human heat shock protein (hsp) 60 elicits a strong proinflammatory response in cells of the innate immune system with CD14, Toll-like receptor (TLR) 2, and TLR4 as mediators of signaling, but probably not of binding. |
| 6 | 11777948 | Hsp60 binding to macrophages could not be competed by excess hsp70, hsp90, or gp96, all of which share the alpha(2)-macroglobulin receptor as binding site. |
| 7 | 11777948 | Hsp60 binding occurred in the absence of surface TLR4. |
| 8 | 11777948 | Previous studies have shown that human heat shock protein (hsp) 60 elicits a strong proinflammatory response in cells of the innate immune system with CD14, Toll-like receptor (TLR) 2, and TLR4 as mediators of signaling, but probably not of binding. |
| 9 | 11777948 | Hsp60 binding to macrophages could not be competed by excess hsp70, hsp90, or gp96, all of which share the alpha(2)-macroglobulin receptor as binding site. |
| 10 | 11777948 | Hsp60 binding occurred in the absence of surface TLR4. |
| 11 | 12594256 | HSP60 strongly stimulated DC for maturation and release of TNF-alpha, IL-12, and IL-1 beta. |
| 12 | 12594256 | However, HSP60 elicited only a weak IL-10 response in DC suggesting a Th1 bias. |
| 13 | 12594256 | Again, a Th1 bias was noted in that cocultures of allogeneic T cells and HSP60-treated DC released IFN-gamma but only small amounts of IL-10 and no detectable IL-4. |
| 14 | 12594256 | Signaling via Toll-like receptor 4 was involved in HSP60-induced cytokine release and maturation because DC of C3H/HeJ mice with a mutant Toll-like receptor 4 showed deficient response to HSP60. |
| 15 | 12594256 | HSP60 was found to rapidly activate the mitogen-activated protein kinases p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase as well as I kappa B in DC. |
| 16 | 15305230 | Toll-like receptor 2 and Toll-like receptor 4 expression in human adrenals. |
| 17 | 15305230 | The newly recognized major role of TLR2 and TLR4 and the adrenal stress response during critical illnesses such as inflammation and sepsis demand comprehensive analysis of their interactions. |
| 18 | 15305230 | Therefore, we analyzed TLR2 and TLR4 expression in human adrenal glands. |
| 19 | 15305230 | Western blot analysis demonstrated the expression of TLR2 and TLR4 in the human adrenocortical cell line NCI-H295. |
| 20 | 15305230 | Immunohistochemical analysis of normal human adrenal glands revealed TLR2 and TLR4 expression in the adrenal cortex, but not in the adrenal medulla. |
| 21 | 15305230 | Toll-like receptor 2 and Toll-like receptor 4 expression in human adrenals. |
| 22 | 15305230 | The newly recognized major role of TLR2 and TLR4 and the adrenal stress response during critical illnesses such as inflammation and sepsis demand comprehensive analysis of their interactions. |
| 23 | 15305230 | Therefore, we analyzed TLR2 and TLR4 expression in human adrenal glands. |
| 24 | 15305230 | Western blot analysis demonstrated the expression of TLR2 and TLR4 in the human adrenocortical cell line NCI-H295. |
| 25 | 15305230 | Immunohistochemical analysis of normal human adrenal glands revealed TLR2 and TLR4 expression in the adrenal cortex, but not in the adrenal medulla. |
| 26 | 15305230 | Toll-like receptor 2 and Toll-like receptor 4 expression in human adrenals. |
| 27 | 15305230 | The newly recognized major role of TLR2 and TLR4 and the adrenal stress response during critical illnesses such as inflammation and sepsis demand comprehensive analysis of their interactions. |
| 28 | 15305230 | Therefore, we analyzed TLR2 and TLR4 expression in human adrenal glands. |
| 29 | 15305230 | Western blot analysis demonstrated the expression of TLR2 and TLR4 in the human adrenocortical cell line NCI-H295. |
| 30 | 15305230 | Immunohistochemical analysis of normal human adrenal glands revealed TLR2 and TLR4 expression in the adrenal cortex, but not in the adrenal medulla. |
| 31 | 15305230 | Toll-like receptor 2 and Toll-like receptor 4 expression in human adrenals. |
| 32 | 15305230 | The newly recognized major role of TLR2 and TLR4 and the adrenal stress response during critical illnesses such as inflammation and sepsis demand comprehensive analysis of their interactions. |
| 33 | 15305230 | Therefore, we analyzed TLR2 and TLR4 expression in human adrenal glands. |
| 34 | 15305230 | Western blot analysis demonstrated the expression of TLR2 and TLR4 in the human adrenocortical cell line NCI-H295. |
| 35 | 15305230 | Immunohistochemical analysis of normal human adrenal glands revealed TLR2 and TLR4 expression in the adrenal cortex, but not in the adrenal medulla. |
| 36 | 15305230 | Toll-like receptor 2 and Toll-like receptor 4 expression in human adrenals. |
| 37 | 15305230 | The newly recognized major role of TLR2 and TLR4 and the adrenal stress response during critical illnesses such as inflammation and sepsis demand comprehensive analysis of their interactions. |
| 38 | 15305230 | Therefore, we analyzed TLR2 and TLR4 expression in human adrenal glands. |
| 39 | 15305230 | Western blot analysis demonstrated the expression of TLR2 and TLR4 in the human adrenocortical cell line NCI-H295. |
| 40 | 15305230 | Immunohistochemical analysis of normal human adrenal glands revealed TLR2 and TLR4 expression in the adrenal cortex, but not in the adrenal medulla. |
| 41 | 16518342 | The objective of this study was to investigate the contribution of TLR4 and MyD88 to acute renal failure (ARF) induced by polymicrobial sepsis. |
| 42 | 16518342 | In summary, ARF induced by polymicrobial sepsis is dependent on MyD88, but not TLR4. |
| 43 | 16518342 | The absence of MyD88 dissociates ARF from liver injury; liver injury is MyD88-independent. |
| 44 | 16518342 | The objective of this study was to investigate the contribution of TLR4 and MyD88 to acute renal failure (ARF) induced by polymicrobial sepsis. |
| 45 | 16518342 | In summary, ARF induced by polymicrobial sepsis is dependent on MyD88, but not TLR4. |
| 46 | 16518342 | The absence of MyD88 dissociates ARF from liver injury; liver injury is MyD88-independent. |
| 47 | 16686757 | RAPA-induced monocyte cell death (RAPA-CD) was impeded by activation of granulocyte macrophage-colony stimulating factor family receptors or toll-like receptor 4, and by exposure to inflammatory cytokines. |
| 48 | 16686757 | In the peripheral blood, CD33(+) and CD14(+) cells decreased, whereas lymphocytes appeared unaffected. |
| 49 | 16686757 | In the bone marrow, myeloid precursors such as CD15(+) and CD15(+)/CD16(+) were selectively and significantly decreased, but no major cytotoxic effects were observed. |
| 50 | 16728431 | Expression of TLR3 and TLR5 was significantly higher in newly diabetic non-obese diabetic (NOD) mice when compared with pre-diabetic and control strains of mice. |
| 51 | 16728431 | Dysregulation of TLR4 expression in the diabetic state correlated with increased nuclear factor kappa B (NF-kappaB) activation in response to the TLR4 ligand LPS and higher expression of IL-12p40, tumor necrosis factor alpha (TNFalpha), IL-6 and inducible nitric oxide synthase but lowered expression of IL-10. |
| 52 | 16728431 | Exposure of bone marrow precursor cells from NOD mice to a hyperglycemic environment during differentiation into macrophages resulted in elevated levels of TLR2 and TLR4 and the cytokine TNFalpha. |
| 53 | 16728431 | Expression of TLR3 and TLR5 was significantly higher in newly diabetic non-obese diabetic (NOD) mice when compared with pre-diabetic and control strains of mice. |
| 54 | 16728431 | Dysregulation of TLR4 expression in the diabetic state correlated with increased nuclear factor kappa B (NF-kappaB) activation in response to the TLR4 ligand LPS and higher expression of IL-12p40, tumor necrosis factor alpha (TNFalpha), IL-6 and inducible nitric oxide synthase but lowered expression of IL-10. |
| 55 | 16728431 | Exposure of bone marrow precursor cells from NOD mice to a hyperglycemic environment during differentiation into macrophages resulted in elevated levels of TLR2 and TLR4 and the cytokine TNFalpha. |
| 56 | 16781673 | Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. |
| 57 | 16781673 | Here, we observed that mRNA level of TLR4 was induced during adipocyte differentiation and remarkably enhanced in fat tissues of obese db/db mice. |
| 58 | 16781673 | In addition, activation of TLR4 with either LPS or free fatty acids stimulated NFkappaB signaling and expression of inflammatory cytokine genes, such as TNFalpha and IL-6 in 3T3-L1 adipocytes. |
| 59 | 16781673 | Furthermore, we discovered that TLR4 activation in 3T3-L1 adipocytes provoked insulin resistance. |
| 60 | 16781673 | Taken together, these results suggest that activation of TLR4 in adipocyte might be implicated in the onset of insulin resistance in obesity and type 2 diabetes. |
| 61 | 16781673 | Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. |
| 62 | 16781673 | Here, we observed that mRNA level of TLR4 was induced during adipocyte differentiation and remarkably enhanced in fat tissues of obese db/db mice. |
| 63 | 16781673 | In addition, activation of TLR4 with either LPS or free fatty acids stimulated NFkappaB signaling and expression of inflammatory cytokine genes, such as TNFalpha and IL-6 in 3T3-L1 adipocytes. |
| 64 | 16781673 | Furthermore, we discovered that TLR4 activation in 3T3-L1 adipocytes provoked insulin resistance. |
| 65 | 16781673 | Taken together, these results suggest that activation of TLR4 in adipocyte might be implicated in the onset of insulin resistance in obesity and type 2 diabetes. |
| 66 | 16781673 | Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. |
| 67 | 16781673 | Here, we observed that mRNA level of TLR4 was induced during adipocyte differentiation and remarkably enhanced in fat tissues of obese db/db mice. |
| 68 | 16781673 | In addition, activation of TLR4 with either LPS or free fatty acids stimulated NFkappaB signaling and expression of inflammatory cytokine genes, such as TNFalpha and IL-6 in 3T3-L1 adipocytes. |
| 69 | 16781673 | Furthermore, we discovered that TLR4 activation in 3T3-L1 adipocytes provoked insulin resistance. |
| 70 | 16781673 | Taken together, these results suggest that activation of TLR4 in adipocyte might be implicated in the onset of insulin resistance in obesity and type 2 diabetes. |
| 71 | 16781673 | Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. |
| 72 | 16781673 | Here, we observed that mRNA level of TLR4 was induced during adipocyte differentiation and remarkably enhanced in fat tissues of obese db/db mice. |
| 73 | 16781673 | In addition, activation of TLR4 with either LPS or free fatty acids stimulated NFkappaB signaling and expression of inflammatory cytokine genes, such as TNFalpha and IL-6 in 3T3-L1 adipocytes. |
| 74 | 16781673 | Furthermore, we discovered that TLR4 activation in 3T3-L1 adipocytes provoked insulin resistance. |
| 75 | 16781673 | Taken together, these results suggest that activation of TLR4 in adipocyte might be implicated in the onset of insulin resistance in obesity and type 2 diabetes. |
| 76 | 16781673 | Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes. |
| 77 | 16781673 | Here, we observed that mRNA level of TLR4 was induced during adipocyte differentiation and remarkably enhanced in fat tissues of obese db/db mice. |
| 78 | 16781673 | In addition, activation of TLR4 with either LPS or free fatty acids stimulated NFkappaB signaling and expression of inflammatory cytokine genes, such as TNFalpha and IL-6 in 3T3-L1 adipocytes. |
| 79 | 16781673 | Furthermore, we discovered that TLR4 activation in 3T3-L1 adipocytes provoked insulin resistance. |
| 80 | 16781673 | Taken together, these results suggest that activation of TLR4 in adipocyte might be implicated in the onset of insulin resistance in obesity and type 2 diabetes. |
| 81 | 16803995 | Results regarding genes involved in inflammation (IL-1 cluster, IL-6, IL-10, TNF-alpha, TGF-beta, TLR-4, PPARgamma), insulin/IGF-1 signaling pathway and lipid metabolism (apolipoproteins, CETP, PON1), and oxidative stress (p53, p66(shc)) will be described. |
| 82 | 16936080 | Analysis of CFH, TLR4, and APOE polymorphism in India suggests the Tyr402His variant of CFH to be a global marker for age-related macular degeneration. |
| 83 | 17094790 | We observed that adiponectin acted as a potent inhibitor of osteoclast formation stimulated by Toll-like receptor 4 (TLR4) ligand and receptor activator of NF-kappaB ligand (RANKL). |
| 84 | 17094790 | Because NF-kappaB is an important transcription factor in osteoclast formation, we examined the effect of adiponectin on its transcriptional activity. |
| 85 | 17094790 | A luciferase assay showed that adiponectin was able to inhibit the TLR4-mediated NF-kappaB activity in RAW264 cells. |
| 86 | 17094790 | In addition, we observed that the cytokine was actually able to inhibit TLR4-mediated expression of the gene for inducible nitric oxide synthase and production of nitric oxide in the cells. |
| 87 | 17094790 | We observed that adiponectin acted as a potent inhibitor of osteoclast formation stimulated by Toll-like receptor 4 (TLR4) ligand and receptor activator of NF-kappaB ligand (RANKL). |
| 88 | 17094790 | Because NF-kappaB is an important transcription factor in osteoclast formation, we examined the effect of adiponectin on its transcriptional activity. |
| 89 | 17094790 | A luciferase assay showed that adiponectin was able to inhibit the TLR4-mediated NF-kappaB activity in RAW264 cells. |
| 90 | 17094790 | In addition, we observed that the cytokine was actually able to inhibit TLR4-mediated expression of the gene for inducible nitric oxide synthase and production of nitric oxide in the cells. |
| 91 | 17094790 | We observed that adiponectin acted as a potent inhibitor of osteoclast formation stimulated by Toll-like receptor 4 (TLR4) ligand and receptor activator of NF-kappaB ligand (RANKL). |
| 92 | 17094790 | Because NF-kappaB is an important transcription factor in osteoclast formation, we examined the effect of adiponectin on its transcriptional activity. |
| 93 | 17094790 | A luciferase assay showed that adiponectin was able to inhibit the TLR4-mediated NF-kappaB activity in RAW264 cells. |
| 94 | 17094790 | In addition, we observed that the cytokine was actually able to inhibit TLR4-mediated expression of the gene for inducible nitric oxide synthase and production of nitric oxide in the cells. |
| 95 | 17130564 | No association of TLR2 and TLR4 polymorphisms with type I diabetes mellitus in the Basque population. |
| 96 | 17130564 | To test the possible role of TLRs in the development of T1DM, we studied different SNPs of TLR2 (N199N, S450S, R677W, and R753Q) and TLR4 (D299G, T399I, and S400N) in Basque families with T1DM. |
| 97 | 17130564 | Genetic association analysis failed to demonstrate any association of these polymorphisms of TLR2 and TLR4 with T1DM in our population. |
| 98 | 17130564 | No association of TLR2 and TLR4 polymorphisms with type I diabetes mellitus in the Basque population. |
| 99 | 17130564 | To test the possible role of TLRs in the development of T1DM, we studied different SNPs of TLR2 (N199N, S450S, R677W, and R753Q) and TLR4 (D299G, T399I, and S400N) in Basque families with T1DM. |
| 100 | 17130564 | Genetic association analysis failed to demonstrate any association of these polymorphisms of TLR2 and TLR4 with T1DM in our population. |
| 101 | 17130564 | No association of TLR2 and TLR4 polymorphisms with type I diabetes mellitus in the Basque population. |
| 102 | 17130564 | To test the possible role of TLRs in the development of T1DM, we studied different SNPs of TLR2 (N199N, S450S, R677W, and R753Q) and TLR4 (D299G, T399I, and S400N) in Basque families with T1DM. |
| 103 | 17130564 | Genetic association analysis failed to demonstrate any association of these polymorphisms of TLR2 and TLR4 with T1DM in our population. |
| 104 | 17202326 | Augmented lipopolysaccharide-induced TNF-alpha production by peritoneal macrophages in type 2 diabetic mice is dependent on elevated glucose and requires p38 MAPK. |
| 105 | 17202326 | In this study, we show that augmented LPS-induced TNF-alpha production by resident peritoneal macrophages (PerMphi) in type 2 diabetic (db/db) mice is dependent on elevated glucose and requires p38 MAPK. |
| 106 | 17202326 | Examination of the TLR-4/MD2 complex and CD14 expression showed no difference between db/db and db/+ PerMphi. |
| 107 | 17202326 | LPS-dependent stimulation of PI3K activity, ERK1/2 activation, and p38 kinase activity was greater in PerMphi from db/db mice as compared with db/+ mice. |
| 108 | 17202326 | Only inhibition of p38 kinase blocked LPS-induced TNF-alpha production in PerMphi from db/db mice. |
| 109 | 17202326 | Taken together, these data indicate that augmented TNF-alpha production induced by LPS in macrophages during diabetes is due to hyperglycemia and increased LPS-dependent activation of p38 kinase. |
| 110 | 17426960 | C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet. |
| 111 | 17475921 | Despite the salutary effects of TLR4 suppression, HO-1 expression is still needed in the recipient for islet survival: TLR4-deficient islets were rejected promptly after being transplanted into recipients in which HO-1 activity was blocked. |
| 112 | 17519423 | Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. |
| 113 | 17519423 | Because it is activated by lipopolysaccharide and saturated fatty acids, which are inducers of insulin resistance, TLR4 may be a candidate for participation in the cross-talk between inflammatory and metabolic signals. |
| 114 | 17519423 | Thus, TLR4 appears to be an important mediator of obesity and insulin resistance and a potential target for the therapy of these highly prevalent medical conditions. |
| 115 | 17519423 | Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. |
| 116 | 17519423 | Because it is activated by lipopolysaccharide and saturated fatty acids, which are inducers of insulin resistance, TLR4 may be a candidate for participation in the cross-talk between inflammatory and metabolic signals. |
| 117 | 17519423 | Thus, TLR4 appears to be an important mediator of obesity and insulin resistance and a potential target for the therapy of these highly prevalent medical conditions. |
| 118 | 17519423 | Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. |
| 119 | 17519423 | Because it is activated by lipopolysaccharide and saturated fatty acids, which are inducers of insulin resistance, TLR4 may be a candidate for participation in the cross-talk between inflammatory and metabolic signals. |
| 120 | 17519423 | Thus, TLR4 appears to be an important mediator of obesity and insulin resistance and a potential target for the therapy of these highly prevalent medical conditions. |
| 121 | 17702846 | We have used U937 cells stably transfected to express luciferase under the control of NF-kappaB to examine if adiponectin may modulate NF-kappaB activity. |
| 122 | 17702846 | Physiological concentrations of native adiponectin induced NF-kappaB activity. |
| 123 | 17702846 | This effect was relatively strong compared with proinflammatory adipokines like leptin, resistin, and IL-6. |
| 124 | 17702846 | The enhanced NF-kappaB activity was attributed to the high molecular weight adiponectin isoforms. |
| 125 | 17702846 | NF-kappaB was not activated by mutated adiponectin that is unable to form high molecular weight complexes. |
| 126 | 17702846 | Furthermore, the C-terminal fragment, globular adiponectin, markedly increased NF-kappaB reporter activity, cytokine release, and mRNA expression of inflammation marker genes, at higher levels than stimulation with TNF-alpha and lipopolysaccharide. |
| 127 | 17702846 | NF-kappaB activation by globular adiponectin was not affected by antibody inhibition of toll-like receptor 4 or TNF receptors 1 and 2 but was attenuated by inhibitors of p38 MAPK, phosphatidylinositol 3-kinase, and protein kinase C. |
| 128 | 17702846 | Analyses of the p65 subunit of NF-kappaB in different leukocyte cell lines showed activation of two monocytic cell lines (U937 and THP-1) by native and globular adiponectin. |
| 129 | 17707128 | The development of autoimmune diabetes was markedly inhibited in Tlr2(-/-) mice but not in Tlr4(-/-) mice, showing that TLR2 plays an important role in the initiation of the disease. |
| 130 | 17707128 | Apoptotic beta-cell injury could stimulate the priming of diabetogenic T cells through a TLR2-dependent, but TLR4-independent, activation of antigen-presenting cells. |
| 131 | 17707128 | The development of autoimmune diabetes was markedly inhibited in Tlr2(-/-) mice but not in Tlr4(-/-) mice, showing that TLR2 plays an important role in the initiation of the disease. |
| 132 | 17707128 | Apoptotic beta-cell injury could stimulate the priming of diabetogenic T cells through a TLR2-dependent, but TLR4-independent, activation of antigen-presenting cells. |
| 133 | 17916553 | Here, we show that FFAs can cause activation of RAW264.7 cells primarily via the JNK signaling cascade and that TLR2 and TLR4 are upstream of JNK and help transduce FFA proinflammatory signals. |
| 134 | 17916553 | In addition, we found that CD11c expression is increased in skeletal muscle of high fat diet-fed mice and that conditioned medium from FFA-treated wild type BMDCs, but not TLR2/4 DKO BMDCs, can induce insulin resistance in L6 myotubes. |
| 135 | 17916553 | Together our results show that FFAs can activate CD11c(+) myeloid proinflammatory cells via TLR2/4 and JNK signaling pathways, thereby promoting inflammation and subsequent cellular insulin resistance. |
| 136 | 17982052 | The TLR4- and MyD88-dependent pathways are required for LPS to shorten allograft survival, whereas polyinosinic:polycytidylic acid mediates its effects through a TLR3-independent pathway. |
| 137 | 17991878 | RNA profiling of lipopolysaccharide-stimulated human MPhi identified CXC chemokine ligands (CXCLs), such as IP-10 (interferon [IFN]-inducible protein 10) (CXCL10), I-TAC (IFN-inducible T-cell alpha chemoattractant) (CXCL11), and Mig (monokine induced by IFN-gamma) (CXCL9), T-lymphocyte chemoattractants associated with atherogenesis, among the top 14 transcripts suppressed by adiponectin. |
| 138 | 17991878 | Adiponectin reduced the release by lipopolysaccharide-stimulated MPhi of chemoattractant activity for CXC chemokine receptor 3-transfected (receptor for IP-10, Mig, and I-TAC) lymphocytes. |
| 139 | 17991878 | Adiponectin decreased lipopolysaccharide-inducible IP-10 promoter activity in promoter-transfected THP-1 MPhi but did not change IP-10 mRNA stability. |
| 140 | 17991878 | In lipopolysaccharide-stimulated MPhi, reduction of IFN-beta by adiponectin preceded inhibition of IP-10 mRNA expression. |
| 141 | 17991878 | Immunoblot and chromatin immunoprecipitation analyses demonstrated that adiponectin attenuated activation of the transcription factor IFN regulatory factor 3, involved in the MyD88-independent pathway of Toll-like receptor 4 signaling, and subsequent IFN regulatory factor 3 binding to IFN-beta promoter. |
| 142 | 17991878 | In vivo studies further demonstrated that apolipoprotein E/adiponectin double-deficient (apoE-/-APN-/-) mice had increased plasma IP-10 levels, accelerated T-lymphocyte accumulation in atheromata, and augmented atherogenesis compared with apoE single-deficient (apoE-/-APN+/+) mice. |
| 143 | 18029440 | We separately overexpressed the p65 subunit of NF-kappaB and IkappaBKbeta in single muscles of rats using in vivo electrotransfer and compared the effects after 1 wk vs. paired contralateral control muscles. |
| 144 | 18029440 | Interestingly, p65 overexpression resulted in a negative feedback reduction of 36% in Toll-like receptor (TLR)-2 (P = 0.03) but not TLR-4 mRNA. |
| 145 | 18633101 | Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. |
| 146 | 18633101 | However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. |
| 147 | 18633101 | We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. |
| 148 | 18633101 | TLR4 muscle protein content correlated with the severity of insulin resistance. |
| 149 | 18633101 | The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. |
| 150 | 18633101 | Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. |
| 151 | 18633101 | Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. |
| 152 | 18633101 | CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans. |
| 153 | 18633101 | Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. |
| 154 | 18633101 | However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. |
| 155 | 18633101 | We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. |
| 156 | 18633101 | TLR4 muscle protein content correlated with the severity of insulin resistance. |
| 157 | 18633101 | The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. |
| 158 | 18633101 | Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. |
| 159 | 18633101 | Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. |
| 160 | 18633101 | CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans. |
| 161 | 18633101 | Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. |
| 162 | 18633101 | However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. |
| 163 | 18633101 | We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. |
| 164 | 18633101 | TLR4 muscle protein content correlated with the severity of insulin resistance. |
| 165 | 18633101 | The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. |
| 166 | 18633101 | Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. |
| 167 | 18633101 | Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. |
| 168 | 18633101 | CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans. |
| 169 | 18633101 | Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. |
| 170 | 18633101 | However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. |
| 171 | 18633101 | We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. |
| 172 | 18633101 | TLR4 muscle protein content correlated with the severity of insulin resistance. |
| 173 | 18633101 | The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. |
| 174 | 18633101 | Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. |
| 175 | 18633101 | Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. |
| 176 | 18633101 | CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans. |
| 177 | 18633101 | Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. |
| 178 | 18633101 | However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. |
| 179 | 18633101 | We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. |
| 180 | 18633101 | TLR4 muscle protein content correlated with the severity of insulin resistance. |
| 181 | 18633101 | The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. |
| 182 | 18633101 | Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. |
| 183 | 18633101 | Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. |
| 184 | 18633101 | CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans. |
| 185 | 18633101 | Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. |
| 186 | 18633101 | However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. |
| 187 | 18633101 | We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. |
| 188 | 18633101 | TLR4 muscle protein content correlated with the severity of insulin resistance. |
| 189 | 18633101 | The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. |
| 190 | 18633101 | Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. |
| 191 | 18633101 | Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. |
| 192 | 18633101 | CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans. |
| 193 | 18633101 | Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. |
| 194 | 18633101 | However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. |
| 195 | 18633101 | We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. |
| 196 | 18633101 | TLR4 muscle protein content correlated with the severity of insulin resistance. |
| 197 | 18633101 | The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. |
| 198 | 18633101 | Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. |
| 199 | 18633101 | Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. |
| 200 | 18633101 | CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans. |
| 201 | 19010563 | CD14, TLR2 and TLR4 expression were analyzed. |
| 202 | 19010563 | Monocytes showed significantly higher surface CD14 expression from LADA compared with that from T2DM and controls, and high expression of TLR4 from LADA and T2DM than controls. |
| 203 | 19010563 | After incubation with LPS or LTA, decreased surface expressions of CD14 were observed on monocytes from T2DM and controls, in contrast to the increased on monocytes from LADA. |
| 204 | 19010563 | Activation of NF-kappaB and amounts of IL-1beta and TNF-alpha production by stimulation with ligands significantly increased in LADA and T2DM, which was modulated by 1,25(OH)(2)D3 to similar level, as compared to controls. |
| 205 | 19010563 | CD14, TLR2 and TLR4 expression were analyzed. |
| 206 | 19010563 | Monocytes showed significantly higher surface CD14 expression from LADA compared with that from T2DM and controls, and high expression of TLR4 from LADA and T2DM than controls. |
| 207 | 19010563 | After incubation with LPS or LTA, decreased surface expressions of CD14 were observed on monocytes from T2DM and controls, in contrast to the increased on monocytes from LADA. |
| 208 | 19010563 | Activation of NF-kappaB and amounts of IL-1beta and TNF-alpha production by stimulation with ligands significantly increased in LADA and T2DM, which was modulated by 1,25(OH)(2)D3 to similar level, as compared to controls. |
| 209 | 19148143 | We aimed to test whether there exist common or inverse associations between polymorphisms in the pattern recognition receptors TLR2, TLR4 and CD14 and T1D and allergic asthma. |
| 210 | 19148143 | Eighteen single nucleotide polymorphisms (SNPs) were genotyped in TLR2 (2), TLR4 (12) and CD14 (4) in 700 T1D children, 357 nuclear families with T1D children and 796 children from the 'Environment and Childhood Asthma' study. |
| 211 | 19148143 | Neither TLR4 nor CD14 were associated with T1D or allergic asthma. |
| 212 | 19148143 | We aimed to test whether there exist common or inverse associations between polymorphisms in the pattern recognition receptors TLR2, TLR4 and CD14 and T1D and allergic asthma. |
| 213 | 19148143 | Eighteen single nucleotide polymorphisms (SNPs) were genotyped in TLR2 (2), TLR4 (12) and CD14 (4) in 700 T1D children, 357 nuclear families with T1D children and 796 children from the 'Environment and Childhood Asthma' study. |
| 214 | 19148143 | Neither TLR4 nor CD14 were associated with T1D or allergic asthma. |
| 215 | 19148143 | We aimed to test whether there exist common or inverse associations between polymorphisms in the pattern recognition receptors TLR2, TLR4 and CD14 and T1D and allergic asthma. |
| 216 | 19148143 | Eighteen single nucleotide polymorphisms (SNPs) were genotyped in TLR2 (2), TLR4 (12) and CD14 (4) in 700 T1D children, 357 nuclear families with T1D children and 796 children from the 'Environment and Childhood Asthma' study. |
| 217 | 19148143 | Neither TLR4 nor CD14 were associated with T1D or allergic asthma. |
| 218 | 19336685 | Comment on: Reyna et al. (2008) Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. |
| 219 | 19395279 | Toll-like receptor 4 and inducible nitric oxide synthase gene polymorphisms are associated with Type 2 diabetes. |
| 220 | 19447045 | Increased secretion of IP-10 from monocytes under hyperglycemia is via the TLR2 and TLR4 pathway. |
| 221 | 19447045 | Among the chemokines, members of the CXC family include IP-10 (interferon-gamma induced protein of 10kDa). |
| 222 | 19447045 | Furthermore, both TLR2 siRNA as well as TLR4 siRNA, either alone or in combination significantly abrogated HG-induced IP-10 release. |
| 223 | 19447045 | Down-regulation of TLR2 and TLR4 abrogates HG-induced IP-10 release via NF-kappaB inhibition. |
| 224 | 19447045 | Increased secretion of IP-10 from monocytes under hyperglycemia is via the TLR2 and TLR4 pathway. |
| 225 | 19447045 | Among the chemokines, members of the CXC family include IP-10 (interferon-gamma induced protein of 10kDa). |
| 226 | 19447045 | Furthermore, both TLR2 siRNA as well as TLR4 siRNA, either alone or in combination significantly abrogated HG-induced IP-10 release. |
| 227 | 19447045 | Down-regulation of TLR2 and TLR4 abrogates HG-induced IP-10 release via NF-kappaB inhibition. |
| 228 | 19447045 | Increased secretion of IP-10 from monocytes under hyperglycemia is via the TLR2 and TLR4 pathway. |
| 229 | 19447045 | Among the chemokines, members of the CXC family include IP-10 (interferon-gamma induced protein of 10kDa). |
| 230 | 19447045 | Furthermore, both TLR2 siRNA as well as TLR4 siRNA, either alone or in combination significantly abrogated HG-induced IP-10 release. |
| 231 | 19447045 | Down-regulation of TLR2 and TLR4 abrogates HG-induced IP-10 release via NF-kappaB inhibition. |
| 232 | 19595807 | Interestingly, in TLRs 1, 2 and 4, which bind lipid ligands using very different interactions from TLR3, the ligands nevertheless promote the formation of a dimer in which the same two lateral surfaces as in the TLR3-ECD:dsRNA complex face each other, bringing their C-termini in close proximity. |
| 233 | 19819943 | Free fatty acids induce a proinflammatory response in islets via the abundantly expressed interleukin-1 receptor I. |
| 234 | 19819943 | IL-1beta is a master regulator of inflammation, and IL-1 receptor type I (IL-1RI) blockage improves glycemia and insulin secretion in humans with T2DM and in high-fat-fed mice pointing to a pivotal role of IL-1RI activity in intra-islet inflammation. |
| 235 | 19819943 | FFA induced IL-1beta, IL-6, and IL-8 in human islets and IL-1beta and KC in mouse islets. |
| 236 | 19819943 | FFA-induced IL-1beta and KC expression in mouse islets was completely dependent on the IL-1R/Toll-like receptor (TLR) docking protein Myd88 and partly dependent on TLR2 and -4. |
| 237 | 19917698 | Activation of TLRs, particularly TLR2 and TLR4, promotes chronic systemic inflammation. |
| 238 | 19917698 | However, recent work showed that an increased percentage of circulating B cells from inflammatory disease patients express TLR2 and TLR4, and that TLR engagement on B cells resulted in unexpected changes in gene expression. |
| 239 | 19917698 | Some cytokines (IL-1beta and IL-10) are predominantly regulated by TLR4, but others (IL-8 and TNF-alpha) are predominantly regulated by TLR2, due in part to TLR-dictated changes in transcription factor/promoter association. |
| 240 | 19917698 | TLR2 and TLR9 also regulate B cell TLR4 expression, demonstrating that TLR cross-talk controls B cell responses at multiple levels. |
| 241 | 19917698 | Activation of TLRs, particularly TLR2 and TLR4, promotes chronic systemic inflammation. |
| 242 | 19917698 | However, recent work showed that an increased percentage of circulating B cells from inflammatory disease patients express TLR2 and TLR4, and that TLR engagement on B cells resulted in unexpected changes in gene expression. |
| 243 | 19917698 | Some cytokines (IL-1beta and IL-10) are predominantly regulated by TLR4, but others (IL-8 and TNF-alpha) are predominantly regulated by TLR2, due in part to TLR-dictated changes in transcription factor/promoter association. |
| 244 | 19917698 | TLR2 and TLR9 also regulate B cell TLR4 expression, demonstrating that TLR cross-talk controls B cell responses at multiple levels. |
| 245 | 20007708 | Adipocyte-mononuclear cell interaction, Toll-like receptor 4 activation, and high glucose synergistically up-regulate osteopontin expression via an interleukin 6-mediated mechanism. |
| 246 | 20007708 | Although it has been reported that osteopontin, a matrix glycoprotein and proinflammatory cytokine, mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance, it remains unclear how osteopontin is up-regulated in adipose tissue in obese humans and animals. |
| 247 | 20007708 | Moreover, lipopolysaccharide or palmitic acid-induced TLR4 activation and high glucose further augmented the coculture-stimulated osteopontin secretion. |
| 248 | 20007708 | In our studies to explore the underlying mechanism, we found that the neutralizing antibodies against interleukin (IL)-6 or IL-6 small interfering RNA transfection in adipocytes effectively inhibited coculture-stimulated osteopontin expression, suggesting that IL-6 released by adipocytes plays an essential role in the coculture-stimulated osteopontin expression by U937 cells. |
| 249 | 20007708 | In conclusion, this study has demonstrated that cell interaction, TLR4 activation, and high glucose up-regulate osteopontin expression, and adipocyte-derived IL-6 played a major role in the up-regulation. |
| 250 | 20007708 | Adipocyte-mononuclear cell interaction, Toll-like receptor 4 activation, and high glucose synergistically up-regulate osteopontin expression via an interleukin 6-mediated mechanism. |
| 251 | 20007708 | Although it has been reported that osteopontin, a matrix glycoprotein and proinflammatory cytokine, mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance, it remains unclear how osteopontin is up-regulated in adipose tissue in obese humans and animals. |
| 252 | 20007708 | Moreover, lipopolysaccharide or palmitic acid-induced TLR4 activation and high glucose further augmented the coculture-stimulated osteopontin secretion. |
| 253 | 20007708 | In our studies to explore the underlying mechanism, we found that the neutralizing antibodies against interleukin (IL)-6 or IL-6 small interfering RNA transfection in adipocytes effectively inhibited coculture-stimulated osteopontin expression, suggesting that IL-6 released by adipocytes plays an essential role in the coculture-stimulated osteopontin expression by U937 cells. |
| 254 | 20007708 | In conclusion, this study has demonstrated that cell interaction, TLR4 activation, and high glucose up-regulate osteopontin expression, and adipocyte-derived IL-6 played a major role in the up-regulation. |
| 255 | 20007708 | Adipocyte-mononuclear cell interaction, Toll-like receptor 4 activation, and high glucose synergistically up-regulate osteopontin expression via an interleukin 6-mediated mechanism. |
| 256 | 20007708 | Although it has been reported that osteopontin, a matrix glycoprotein and proinflammatory cytokine, mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance, it remains unclear how osteopontin is up-regulated in adipose tissue in obese humans and animals. |
| 257 | 20007708 | Moreover, lipopolysaccharide or palmitic acid-induced TLR4 activation and high glucose further augmented the coculture-stimulated osteopontin secretion. |
| 258 | 20007708 | In our studies to explore the underlying mechanism, we found that the neutralizing antibodies against interleukin (IL)-6 or IL-6 small interfering RNA transfection in adipocytes effectively inhibited coculture-stimulated osteopontin expression, suggesting that IL-6 released by adipocytes plays an essential role in the coculture-stimulated osteopontin expression by U937 cells. |
| 259 | 20007708 | In conclusion, this study has demonstrated that cell interaction, TLR4 activation, and high glucose up-regulate osteopontin expression, and adipocyte-derived IL-6 played a major role in the up-regulation. |
| 260 | 20067961 | Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling-3. |
| 261 | 20124731 | Treatment with an HMGB1-specific antibody prevented the early islet graft loss and inhibited IFN-gamma production by NKT cells and Gr-1(+)CD11b(+) cells. |
| 262 | 20124731 | Moreover, mice lacking either of the known HMGB1 receptors TLR2 or receptor for advanced glycation end products (RAGE), but not the known HMGB1 receptor TLR4, failed to exhibit early islet graft loss. |
| 263 | 20124731 | Mechanistically, HMGB1 stimulated hepatic mononuclear cells (MNCs) in vivo and in vitro; in particular, it upregulated CD40 expression and enhanced IL-12 production by DCs, leading to NKT cell activation and subsequent NKT cell-dependent augmented IFN-gamma production by Gr-1(+)CD11b(+) cells. |
| 264 | 20124731 | Thus, treatment with either IL-12- or CD40L-specific antibody prevented the early islet graft loss. |
| 265 | 20153491 | Demonstration of increased toll-like receptor 2 and toll-like receptor 4 expression in monocytes of type 1 diabetes mellitus patients with microvascular complications. |
| 266 | 20153491 | We have shown increased TLR2 and TLR4 expression on monocytes of T1DM compared with controls. |
| 267 | 20153491 | In this report, we tested the surface expression of TLR2 and TLR4 on monocytes of T1DM patients with microvascular complications (T1DM-MV) compared with those without (T1DM) and healthy controls. |
| 268 | 20153491 | The TLR2 and TLR4 surface expression was significantly increased in T1DM-MV monocytes compared with T1DM and controls (P < .01). |
| 269 | 20153491 | Thus, we make the novel observation that TLR2 and TLR4 expression and signaling are increased in T1DM-MV compared with T1DM and may contribute to the accentuated proinflammatory state and complications of T1DM. |
| 270 | 20153491 | Demonstration of increased toll-like receptor 2 and toll-like receptor 4 expression in monocytes of type 1 diabetes mellitus patients with microvascular complications. |
| 271 | 20153491 | We have shown increased TLR2 and TLR4 expression on monocytes of T1DM compared with controls. |
| 272 | 20153491 | In this report, we tested the surface expression of TLR2 and TLR4 on monocytes of T1DM patients with microvascular complications (T1DM-MV) compared with those without (T1DM) and healthy controls. |
| 273 | 20153491 | The TLR2 and TLR4 surface expression was significantly increased in T1DM-MV monocytes compared with T1DM and controls (P < .01). |
| 274 | 20153491 | Thus, we make the novel observation that TLR2 and TLR4 expression and signaling are increased in T1DM-MV compared with T1DM and may contribute to the accentuated proinflammatory state and complications of T1DM. |
| 275 | 20153491 | Demonstration of increased toll-like receptor 2 and toll-like receptor 4 expression in monocytes of type 1 diabetes mellitus patients with microvascular complications. |
| 276 | 20153491 | We have shown increased TLR2 and TLR4 expression on monocytes of T1DM compared with controls. |
| 277 | 20153491 | In this report, we tested the surface expression of TLR2 and TLR4 on monocytes of T1DM patients with microvascular complications (T1DM-MV) compared with those without (T1DM) and healthy controls. |
| 278 | 20153491 | The TLR2 and TLR4 surface expression was significantly increased in T1DM-MV monocytes compared with T1DM and controls (P < .01). |
| 279 | 20153491 | Thus, we make the novel observation that TLR2 and TLR4 expression and signaling are increased in T1DM-MV compared with T1DM and may contribute to the accentuated proinflammatory state and complications of T1DM. |
| 280 | 20153491 | Demonstration of increased toll-like receptor 2 and toll-like receptor 4 expression in monocytes of type 1 diabetes mellitus patients with microvascular complications. |
| 281 | 20153491 | We have shown increased TLR2 and TLR4 expression on monocytes of T1DM compared with controls. |
| 282 | 20153491 | In this report, we tested the surface expression of TLR2 and TLR4 on monocytes of T1DM patients with microvascular complications (T1DM-MV) compared with those without (T1DM) and healthy controls. |
| 283 | 20153491 | The TLR2 and TLR4 surface expression was significantly increased in T1DM-MV monocytes compared with T1DM and controls (P < .01). |
| 284 | 20153491 | Thus, we make the novel observation that TLR2 and TLR4 expression and signaling are increased in T1DM-MV compared with T1DM and may contribute to the accentuated proinflammatory state and complications of T1DM. |
| 285 | 20153491 | Demonstration of increased toll-like receptor 2 and toll-like receptor 4 expression in monocytes of type 1 diabetes mellitus patients with microvascular complications. |
| 286 | 20153491 | We have shown increased TLR2 and TLR4 expression on monocytes of T1DM compared with controls. |
| 287 | 20153491 | In this report, we tested the surface expression of TLR2 and TLR4 on monocytes of T1DM patients with microvascular complications (T1DM-MV) compared with those without (T1DM) and healthy controls. |
| 288 | 20153491 | The TLR2 and TLR4 surface expression was significantly increased in T1DM-MV monocytes compared with T1DM and controls (P < .01). |
| 289 | 20153491 | Thus, we make the novel observation that TLR2 and TLR4 expression and signaling are increased in T1DM-MV compared with T1DM and may contribute to the accentuated proinflammatory state and complications of T1DM. |
| 290 | 20179247 | Toll-like receptor 4 (TLR4), a protein integral to innate immunity, is elevated in skeletal muscle of obese and type 2 diabetic humans and has been implicated in the development of lipid-induced insulin resistance. |
| 291 | 20179247 | The purpose of this study was to examine the role of TLR4 as a modulator of basal (non-insulin-stimulated) substrate metabolism in skeletal muscle with the hypothesis that its activation would result in reduced fatty acid oxidation and increased partitioning of fatty acids toward neutral lipid storage. |
| 292 | 20179247 | Toll-like receptor 4 (TLR4), a protein integral to innate immunity, is elevated in skeletal muscle of obese and type 2 diabetic humans and has been implicated in the development of lipid-induced insulin resistance. |
| 293 | 20179247 | The purpose of this study was to examine the role of TLR4 as a modulator of basal (non-insulin-stimulated) substrate metabolism in skeletal muscle with the hypothesis that its activation would result in reduced fatty acid oxidation and increased partitioning of fatty acids toward neutral lipid storage. |
| 294 | 20483368 | We performed copy number analysis of TLR2, TLR4, and the beta-defensin cluster (DEFB4, DEFB103 and DEFB104) by gene-specific, real-time polymerase chain reaction (PCR) in 376 CD patients and 376 controls. |
| 295 | 20674989 | TLR4 is expressed in pancreatic β-cells of rodents and humans and its stimulation affects insulin secretion in response to glucose. |
| 296 | 20725710 | We also found that TLR4 activation induced a higher frequency of IL-1β expressing monocytes and a reduction in the percentage of IL-6 expressing myeloid dendritic cells (mDCs). |
| 297 | 20725710 | The altered TLR responsiveness was not due to aberrant proportions of peripheral DC subsets and monocytes in the blood and did not correlate with altered hemoglobin A1c and the expression of diabetes susceptibility genes but could potentially be associated with enhanced nuclear factor-kappa B signaling. |
| 298 | 20725710 | Finally, we observed that levels of serum IFN-α2, IL-1β, IFN-γ, and CXCL-10 were elevated in new onset patients versus the control group. |
| 299 | 20809521 | Islet-expressed TLR2 and TLR4 sense injury and mediate early graft failure after transplantation. |
| 300 | 20809521 | Murine islets constitutively express TLR2 and TLR4, and TLR activation with peptidoglycan or LPS upregulates islet production of cytokines and chemokines. |
| 301 | 20809521 | Stressed islets released the alarmin high-mobility group box protein 1 (HMGB1) and recombinant HMGB1 (rHMGB1) induced NFkB activation. |
| 302 | 20809521 | NFkB activation was prevented in the absence of both TLR2 and TLR4. rHMGB1 pretreatment also prevented primary engraftment through a TLR2/4-dependent pathway. |
| 303 | 20809521 | Our results show that islet graft failure can be initiated by TLR2 and TLR4 signaling and suggest that HMGB1 is one likely early mediator. |
| 304 | 20809521 | Islet-expressed TLR2 and TLR4 sense injury and mediate early graft failure after transplantation. |
| 305 | 20809521 | Murine islets constitutively express TLR2 and TLR4, and TLR activation with peptidoglycan or LPS upregulates islet production of cytokines and chemokines. |
| 306 | 20809521 | Stressed islets released the alarmin high-mobility group box protein 1 (HMGB1) and recombinant HMGB1 (rHMGB1) induced NFkB activation. |
| 307 | 20809521 | NFkB activation was prevented in the absence of both TLR2 and TLR4. rHMGB1 pretreatment also prevented primary engraftment through a TLR2/4-dependent pathway. |
| 308 | 20809521 | Our results show that islet graft failure can be initiated by TLR2 and TLR4 signaling and suggest that HMGB1 is one likely early mediator. |
| 309 | 20809521 | Islet-expressed TLR2 and TLR4 sense injury and mediate early graft failure after transplantation. |
| 310 | 20809521 | Murine islets constitutively express TLR2 and TLR4, and TLR activation with peptidoglycan or LPS upregulates islet production of cytokines and chemokines. |
| 311 | 20809521 | Stressed islets released the alarmin high-mobility group box protein 1 (HMGB1) and recombinant HMGB1 (rHMGB1) induced NFkB activation. |
| 312 | 20809521 | NFkB activation was prevented in the absence of both TLR2 and TLR4. rHMGB1 pretreatment also prevented primary engraftment through a TLR2/4-dependent pathway. |
| 313 | 20809521 | Our results show that islet graft failure can be initiated by TLR2 and TLR4 signaling and suggest that HMGB1 is one likely early mediator. |
| 314 | 20809521 | Islet-expressed TLR2 and TLR4 sense injury and mediate early graft failure after transplantation. |
| 315 | 20809521 | Murine islets constitutively express TLR2 and TLR4, and TLR activation with peptidoglycan or LPS upregulates islet production of cytokines and chemokines. |
| 316 | 20809521 | Stressed islets released the alarmin high-mobility group box protein 1 (HMGB1) and recombinant HMGB1 (rHMGB1) induced NFkB activation. |
| 317 | 20809521 | NFkB activation was prevented in the absence of both TLR2 and TLR4. rHMGB1 pretreatment also prevented primary engraftment through a TLR2/4-dependent pathway. |
| 318 | 20809521 | Our results show that islet graft failure can be initiated by TLR2 and TLR4 signaling and suggest that HMGB1 is one likely early mediator. |
| 319 | 20853621 | The data of TLR-4 and TLR-2 existance in adipose tissue cells is presented in the review, their signal pathway is described, and an idea of physiological and pathological role of innate immune system receptors is given proof. |
| 320 | 20876708 | Animals models of obesity connect an altered microbiota composition to the development of obesity, insulin resistance, and diabetes in the host through several mechanisms: increased energy harvest from the diet, altered fatty acid metabolism and composition in adipose tissue and liver, modulation of gut peptide YY and glucagon-like peptide (GLP)-1 secretion, activation of the lipopolysaccharide toll-like receptor-4 axis, and modulation of intestinal barrier integrity by GLP-2. |
| 321 | 20959532 | THP-1 monocytic cells, CD14(+) human monocytes, and transiently transfected HEK293 cells were exposed to various FFA (0-500 μM) and glucose (5-20 mM) for evaluation of TLR2, TLR4, NF-κB, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and superoxide release. |
| 322 | 20959532 | In THP-1 cells, palmitate increased cellular TLR2 and TLR4 expression, generated reactive oxygen species (ROS), and increased NF-κB activity, IL-1β, and MCP-1 release in a dose- and time-dependent manner. |
| 323 | 20959532 | Silencing TLR2, TLR4, and p47phox with small inhibitory RNAs (siRNAs) significantly reduced superoxide release, NF-κB activity, IL-1β, and MCP-1 secretion in HG and palmitate-treated THP-1 cells. |
| 324 | 20959532 | Moreover, data from transient transfection experiments suggest that TLR6 is required for TLR2 and MD2 for TLR4 to augment inflammation in FFA- and glucose-exposed cells. |
| 325 | 20959532 | THP-1 monocytic cells, CD14(+) human monocytes, and transiently transfected HEK293 cells were exposed to various FFA (0-500 μM) and glucose (5-20 mM) for evaluation of TLR2, TLR4, NF-κB, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and superoxide release. |
| 326 | 20959532 | In THP-1 cells, palmitate increased cellular TLR2 and TLR4 expression, generated reactive oxygen species (ROS), and increased NF-κB activity, IL-1β, and MCP-1 release in a dose- and time-dependent manner. |
| 327 | 20959532 | Silencing TLR2, TLR4, and p47phox with small inhibitory RNAs (siRNAs) significantly reduced superoxide release, NF-κB activity, IL-1β, and MCP-1 secretion in HG and palmitate-treated THP-1 cells. |
| 328 | 20959532 | Moreover, data from transient transfection experiments suggest that TLR6 is required for TLR2 and MD2 for TLR4 to augment inflammation in FFA- and glucose-exposed cells. |
| 329 | 20959532 | THP-1 monocytic cells, CD14(+) human monocytes, and transiently transfected HEK293 cells were exposed to various FFA (0-500 μM) and glucose (5-20 mM) for evaluation of TLR2, TLR4, NF-κB, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and superoxide release. |
| 330 | 20959532 | In THP-1 cells, palmitate increased cellular TLR2 and TLR4 expression, generated reactive oxygen species (ROS), and increased NF-κB activity, IL-1β, and MCP-1 release in a dose- and time-dependent manner. |
| 331 | 20959532 | Silencing TLR2, TLR4, and p47phox with small inhibitory RNAs (siRNAs) significantly reduced superoxide release, NF-κB activity, IL-1β, and MCP-1 secretion in HG and palmitate-treated THP-1 cells. |
| 332 | 20959532 | Moreover, data from transient transfection experiments suggest that TLR6 is required for TLR2 and MD2 for TLR4 to augment inflammation in FFA- and glucose-exposed cells. |
| 333 | 20959532 | THP-1 monocytic cells, CD14(+) human monocytes, and transiently transfected HEK293 cells were exposed to various FFA (0-500 μM) and glucose (5-20 mM) for evaluation of TLR2, TLR4, NF-κB, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and superoxide release. |
| 334 | 20959532 | In THP-1 cells, palmitate increased cellular TLR2 and TLR4 expression, generated reactive oxygen species (ROS), and increased NF-κB activity, IL-1β, and MCP-1 release in a dose- and time-dependent manner. |
| 335 | 20959532 | Silencing TLR2, TLR4, and p47phox with small inhibitory RNAs (siRNAs) significantly reduced superoxide release, NF-κB activity, IL-1β, and MCP-1 secretion in HG and palmitate-treated THP-1 cells. |
| 336 | 20959532 | Moreover, data from transient transfection experiments suggest that TLR6 is required for TLR2 and MD2 for TLR4 to augment inflammation in FFA- and glucose-exposed cells. |
| 337 | 21088297 | This study investigates the role of peroxisome proliferator-activated receptor γ (PPAR γ) and lanthionine synthetase C-like 2 (LANCL2) as molecular targets for ABA. |
| 338 | 21088297 | LANCL2 knockdown studies provide evidence that ABA-mediated activation of macrophage PPAR γ is dependent on lancl2 expression. |
| 339 | 21088297 | ABA suppresses LPS-induced prostaglandin E(2) and MCP-1 production via a PPAR γ-dependent mechanism possibly involving activation of PPAR γ and suppression of NF-κB and nuclear factor of activated T cells. |
| 340 | 21088297 | LPS challenge studies in PPAR γ-expressing and immune cell-specific PPAR γ null mice demonstrate that ABA down-regulates toll-like receptor 4 expression in macrophages and T cells in vivo through a PPAR γ-dependent mechanism. |
| 341 | 21088297 | In conclusion, ABA decreases LPS-mediated inflammation and regulates innate immune responses through a bifurcating pathway involving LANCL2 and an alternative, ligand-binding domain-independent mechanism of PPAR γ activation. |
| 342 | 21099280 | We have identified the Toll like receptor 4 as the receptor for CXCL10 and as new pathway for the induction of β-cell apoptosis. |
| 343 | 21099302 | We examined the role of the TIR-domain containing adaptor-inducing interferon-β (TRIF or TICAM-1), a major signaling molecule for TLR3 and TLR4, in b-cell function and glucose homeostasis by examining mice lacking TRIF (Trif⁻(/)⁻), TLR3 (Tlr3⁻(/)⁻) or TLR4 (Tlr4⁻(/)⁻). |
| 344 | 21215754 | Expression of toll-like receptor-4 (TLR-4), phosphorylation of c-Jun N-terminal kinase (JNK), and nuclear fraction of NF-κB p65 were also significantly lower in MIF KO hearts with I/R. |
| 345 | 21248167 | Hyaluronan fragments signal through both Toll-like receptor (TLR) 4 and TLR2 as well as CD44 to stimulate inflammatory genes in inflammatory cells. |
| 346 | 21248167 | Hyaluronan is also present on the cell surface of epithelial cells and provides protection against tissue damage from the environment by interacting with TLR2 and TLR4. |
| 347 | 21350098 | There was a significant negative correlation between vitamin D levels and high-sensitivity C-reactive protein, NFκB activity, and TLR4 expression (P < .05). |
| 348 | 21439567 | However, the origin and nature of the agents responsible for stimulating TLR2 or TLR4 signalling in these conditions remain to be clearly identified. |
| 349 | 21439567 | This review summarises the evidence supporting the proposal that 'pathogen-associated molecular patterns' (PAMPs) derived from dietary and commensal sources may contribute to the chronic inflammatory processes that underpin the development of these diseases via stimulation of TLR2 and TLR4. |
| 350 | 21439567 | However, the origin and nature of the agents responsible for stimulating TLR2 or TLR4 signalling in these conditions remain to be clearly identified. |
| 351 | 21439567 | This review summarises the evidence supporting the proposal that 'pathogen-associated molecular patterns' (PAMPs) derived from dietary and commensal sources may contribute to the chronic inflammatory processes that underpin the development of these diseases via stimulation of TLR2 and TLR4. |
| 352 | 21498084 | Recent findings have shown increased TLR2 and 4 expression, signaling, ligands, and functional activation in T1DM subjects compared to controls and further accentuated in T1DM with microvascular complications. |
| 353 | 21498084 | Diabetic (WT+STZ) mice had increased expression of both TLR2 and TLR4, while TLR4(-/-) STZ mice had increased expression only of TLR2, but not TLR4 compared to the non-diabetic mice TLR2 expression was significantly increased with STZ-induced diabetes and was unaffected by knockout of TLR4. |
| 354 | 21498084 | Also, levels of MyD88, IRAK-1 protein phosphorylation, Trif, IRF3, and NF-κB activity were significantly reduced in TLR4(-/-) +STZ mice compared to the WT+STZ mice. |
| 355 | 21498084 | WT+STZ mice exhibited significantly increased levels of serum and macrophage IL-1β, IL-6, KC/IL-8, IP-10, MCP-1, IFN beta and TNF-α compared to WT mice and this was significantly attenuated in TLR4(-/-) +STZ mice (P<0.01). |
| 356 | 21498084 | Recent findings have shown increased TLR2 and 4 expression, signaling, ligands, and functional activation in T1DM subjects compared to controls and further accentuated in T1DM with microvascular complications. |
| 357 | 21498084 | Diabetic (WT+STZ) mice had increased expression of both TLR2 and TLR4, while TLR4(-/-) STZ mice had increased expression only of TLR2, but not TLR4 compared to the non-diabetic mice TLR2 expression was significantly increased with STZ-induced diabetes and was unaffected by knockout of TLR4. |
| 358 | 21498084 | Also, levels of MyD88, IRAK-1 protein phosphorylation, Trif, IRF3, and NF-κB activity were significantly reduced in TLR4(-/-) +STZ mice compared to the WT+STZ mice. |
| 359 | 21498084 | WT+STZ mice exhibited significantly increased levels of serum and macrophage IL-1β, IL-6, KC/IL-8, IP-10, MCP-1, IFN beta and TNF-α compared to WT mice and this was significantly attenuated in TLR4(-/-) +STZ mice (P<0.01). |
| 360 | 21498084 | Recent findings have shown increased TLR2 and 4 expression, signaling, ligands, and functional activation in T1DM subjects compared to controls and further accentuated in T1DM with microvascular complications. |
| 361 | 21498084 | Diabetic (WT+STZ) mice had increased expression of both TLR2 and TLR4, while TLR4(-/-) STZ mice had increased expression only of TLR2, but not TLR4 compared to the non-diabetic mice TLR2 expression was significantly increased with STZ-induced diabetes and was unaffected by knockout of TLR4. |
| 362 | 21498084 | Also, levels of MyD88, IRAK-1 protein phosphorylation, Trif, IRF3, and NF-κB activity were significantly reduced in TLR4(-/-) +STZ mice compared to the WT+STZ mice. |
| 363 | 21498084 | WT+STZ mice exhibited significantly increased levels of serum and macrophage IL-1β, IL-6, KC/IL-8, IP-10, MCP-1, IFN beta and TNF-α compared to WT mice and this was significantly attenuated in TLR4(-/-) +STZ mice (P<0.01). |
| 364 | 21498084 | Recent findings have shown increased TLR2 and 4 expression, signaling, ligands, and functional activation in T1DM subjects compared to controls and further accentuated in T1DM with microvascular complications. |
| 365 | 21498084 | Diabetic (WT+STZ) mice had increased expression of both TLR2 and TLR4, while TLR4(-/-) STZ mice had increased expression only of TLR2, but not TLR4 compared to the non-diabetic mice TLR2 expression was significantly increased with STZ-induced diabetes and was unaffected by knockout of TLR4. |
| 366 | 21498084 | Also, levels of MyD88, IRAK-1 protein phosphorylation, Trif, IRF3, and NF-κB activity were significantly reduced in TLR4(-/-) +STZ mice compared to the WT+STZ mice. |
| 367 | 21498084 | WT+STZ mice exhibited significantly increased levels of serum and macrophage IL-1β, IL-6, KC/IL-8, IP-10, MCP-1, IFN beta and TNF-α compared to WT mice and this was significantly attenuated in TLR4(-/-) +STZ mice (P<0.01). |
| 368 | 21503675 | Concomitant with TLR/MyD88 interaction, the level of phospho-C-Jun N-terminal kinase (phospho-JNK) showed an increase; however, the level of inhibitory factor kappa B alpha (IκBα) showed a decrease. |
| 369 | 21503675 | Gene knockdown of TLR4 prevented palmitate-induced INS-1 cell death, while knockdown of TLR2 did not. |
| 370 | 21503675 | These data suggest involvement of JNK activation through the TLR4 signaling pathway in palmitate-induced INS-1 beta cell death. |
| 371 | 21503675 | Concomitant with TLR/MyD88 interaction, the level of phospho-C-Jun N-terminal kinase (phospho-JNK) showed an increase; however, the level of inhibitory factor kappa B alpha (IκBα) showed a decrease. |
| 372 | 21503675 | Gene knockdown of TLR4 prevented palmitate-induced INS-1 cell death, while knockdown of TLR2 did not. |
| 373 | 21503675 | These data suggest involvement of JNK activation through the TLR4 signaling pathway in palmitate-induced INS-1 beta cell death. |
| 374 | 21558879 | DPP-4 (CD26) inhibitor alogliptin inhibits atherosclerosis in diabetic apolipoprotein E-deficient mice. |
| 375 | 21558879 | In this study, nondiabetic and diabetic apolipoprotein E-deficient mice were treated with DPP-4 inhibitor alogliptin for 24 weeks, and atherosclerotic lesions in aortic origins were examined. |
| 376 | 21558879 | Furthermore, immunohistochemistry study showed that diabetes increased interleukin-6 (IL-6) and IL-1β protein expression in atherosclerotic plaques, but alogliptin treatment attenuated diabetes-augmented IL-6 and IL-1β expression. |
| 377 | 21558879 | In consistence with the observations from the mouse models, our in vitro studies showed that alogliptin-inhibited toll-like receptor 4 (TLR-4)-mediated upregulation of IL-6, IL-1β, and other proinflammatory cytokines by mononuclear cells. |
| 378 | 21560483 | Increasing numbers of endogenous danger signals of host origin are being identified including, for example, uric acid and cholesterol crystals, high mobility group box1 (HMGB1) protein, oxidized LDL, vesicans, heat shock proteins (HSPs) and self DNA. |
| 379 | 21560483 | Moreover, some PRRs (e.g., TLR2,TLR4 and NLRP3) and atypical PRRs can recognize both PAMPs and DAMPs, either as single entities or after forming complexes (e.g., immune complexes, or DNA- HMGB1 and DNA-LL37 complexes), so there must be a mechanism to selectively depress or alleviate the inflammatory response to DAMPs, while leaving that of PAMPs intact. |
| 380 | 21560483 | For example, CD24 reacting with HMGB1 and HSPs has been implicated to function as negative regulator for RAGE. |
| 381 | 21565193 | Inroads into the understanding of the relationship between metabolic pathways and inflammation are indicating that signaling by innate immune receptors such as TLR4 and Nlrp3 regulate metabolism. |
| 382 | 21565193 | TLRs have been shown to promote glycolysis, whilst Nlrp3-mediated production of IL-1β causes insulin resistance. |
| 383 | 21677444 | Renal TLR4 mRNA expression correlates with inflammatory marker MCP-1 and profibrotic molecule TGF-β₁ in patients with chronic kidney disease. |
| 384 | 21700474 | PPARγ agonist rosiglitazone ameliorates LPS-induced inflammation in vascular smooth muscle cells via the TLR4/TRIF/IRF3/IP-10 signaling pathway. |
| 385 | 21700474 | The current study demonstrated that rosiglitazone exerted a potent anti-inflammatory action via decreasing interleukin-18 (IL-18), tissue inhibitor of metalloproteinase-1 (TIMP-1), TLR4 and increasing PPARγ in LPS-induced VSMCs. |
| 386 | 21700474 | Interestingly, the results indicated that beneficial effects of rosiglitazone on LPS-induced inflammation in VSMCs were mediated via interference of TLR4 and its downstream signaling components including Toll-interleukin-1 (IL-1) receptor domain-containing adaptor inducing interferon-β (TRIF), interferon regulatory factor 3 (IRF3) and interferon-gamma inducible protein 10 (IP-10). |
| 387 | 21700474 | More importantly, the regulation of the TRIF-dependent TLR4 signaling pathway (TLR4/TRIF/ IRF3/IP-10) provides new insight to understand the mode of action of rosiglitazone for its anti-inflammatory effects. |
| 388 | 21700474 | PPARγ agonist rosiglitazone ameliorates LPS-induced inflammation in vascular smooth muscle cells via the TLR4/TRIF/IRF3/IP-10 signaling pathway. |
| 389 | 21700474 | The current study demonstrated that rosiglitazone exerted a potent anti-inflammatory action via decreasing interleukin-18 (IL-18), tissue inhibitor of metalloproteinase-1 (TIMP-1), TLR4 and increasing PPARγ in LPS-induced VSMCs. |
| 390 | 21700474 | Interestingly, the results indicated that beneficial effects of rosiglitazone on LPS-induced inflammation in VSMCs were mediated via interference of TLR4 and its downstream signaling components including Toll-interleukin-1 (IL-1) receptor domain-containing adaptor inducing interferon-β (TRIF), interferon regulatory factor 3 (IRF3) and interferon-gamma inducible protein 10 (IP-10). |
| 391 | 21700474 | More importantly, the regulation of the TRIF-dependent TLR4 signaling pathway (TLR4/TRIF/ IRF3/IP-10) provides new insight to understand the mode of action of rosiglitazone for its anti-inflammatory effects. |
| 392 | 21700474 | PPARγ agonist rosiglitazone ameliorates LPS-induced inflammation in vascular smooth muscle cells via the TLR4/TRIF/IRF3/IP-10 signaling pathway. |
| 393 | 21700474 | The current study demonstrated that rosiglitazone exerted a potent anti-inflammatory action via decreasing interleukin-18 (IL-18), tissue inhibitor of metalloproteinase-1 (TIMP-1), TLR4 and increasing PPARγ in LPS-induced VSMCs. |
| 394 | 21700474 | Interestingly, the results indicated that beneficial effects of rosiglitazone on LPS-induced inflammation in VSMCs were mediated via interference of TLR4 and its downstream signaling components including Toll-interleukin-1 (IL-1) receptor domain-containing adaptor inducing interferon-β (TRIF), interferon regulatory factor 3 (IRF3) and interferon-gamma inducible protein 10 (IP-10). |
| 395 | 21700474 | More importantly, the regulation of the TRIF-dependent TLR4 signaling pathway (TLR4/TRIF/ IRF3/IP-10) provides new insight to understand the mode of action of rosiglitazone for its anti-inflammatory effects. |
| 396 | 21700474 | PPARγ agonist rosiglitazone ameliorates LPS-induced inflammation in vascular smooth muscle cells via the TLR4/TRIF/IRF3/IP-10 signaling pathway. |
| 397 | 21700474 | The current study demonstrated that rosiglitazone exerted a potent anti-inflammatory action via decreasing interleukin-18 (IL-18), tissue inhibitor of metalloproteinase-1 (TIMP-1), TLR4 and increasing PPARγ in LPS-induced VSMCs. |
| 398 | 21700474 | Interestingly, the results indicated that beneficial effects of rosiglitazone on LPS-induced inflammation in VSMCs were mediated via interference of TLR4 and its downstream signaling components including Toll-interleukin-1 (IL-1) receptor domain-containing adaptor inducing interferon-β (TRIF), interferon regulatory factor 3 (IRF3) and interferon-gamma inducible protein 10 (IP-10). |
| 399 | 21700474 | More importantly, the regulation of the TRIF-dependent TLR4 signaling pathway (TLR4/TRIF/ IRF3/IP-10) provides new insight to understand the mode of action of rosiglitazone for its anti-inflammatory effects. |
| 400 | 21813778 | IL-1 blockade attenuates islet amyloid polypeptide-induced proinflammatory cytokine release and pancreatic islet graft dysfunction. |
| 401 | 21813778 | We sought to determine whether human islet amyloid polypeptide (hIAPP), the main component of islet amyloid, might contribute to islet inflammation by recruiting and activating macrophages. |
| 402 | 21813778 | Early aggregates of hIAPP, but not nonamyloidogenic rodent islet amyloid polypeptide, caused release of CCL2 and CXCL1 by islets and induced secretion of TNF-α, IL-1α, IL-1β, CCL2, CCL3, CXCL1, CXCL2, and CXCL10 by C57BL/6 bone marrow-derived macrophages. hIAPP-induced TNF-α secretion was markedly diminished in MyD88-, but not TLR2- or TLR4-deficient macrophages, and in cells treated with the IL-1R antagonist (IL-1Ra) anakinra. |
| 403 | 21813778 | Our results suggest that hIAPP-induced islet chemokine secretion promotes macrophage recruitment and that IL-1R/MyD88, but not TLR2 or TLR4 signaling is required for maximal macrophage responsiveness to prefibrillar hIAPP. |
| 404 | 21813778 | IL-1 blockade attenuates islet amyloid polypeptide-induced proinflammatory cytokine release and pancreatic islet graft dysfunction. |
| 405 | 21813778 | We sought to determine whether human islet amyloid polypeptide (hIAPP), the main component of islet amyloid, might contribute to islet inflammation by recruiting and activating macrophages. |
| 406 | 21813778 | Early aggregates of hIAPP, but not nonamyloidogenic rodent islet amyloid polypeptide, caused release of CCL2 and CXCL1 by islets and induced secretion of TNF-α, IL-1α, IL-1β, CCL2, CCL3, CXCL1, CXCL2, and CXCL10 by C57BL/6 bone marrow-derived macrophages. hIAPP-induced TNF-α secretion was markedly diminished in MyD88-, but not TLR2- or TLR4-deficient macrophages, and in cells treated with the IL-1R antagonist (IL-1Ra) anakinra. |
| 407 | 21813778 | Our results suggest that hIAPP-induced islet chemokine secretion promotes macrophage recruitment and that IL-1R/MyD88, but not TLR2 or TLR4 signaling is required for maximal macrophage responsiveness to prefibrillar hIAPP. |
| 408 | 21847775 | Proinflammatory CD14+CD16+ monocytes are associated with microinflammation in patients with type 2 diabetes mellitus and diabetic nephropathy uremia. |
| 409 | 21847775 | In this study, we investigated the expression of Toll-like receptor 4 (TLR4) and CD14(+)CD16(+) monocytes in patients with T2DM and DN patients with uremia and TLR4 response to lipopolysaccharide (LPS), and to further explore the potential effects of inflammatory immune response in T2DM and DN uremia. |
| 410 | 21847775 | Thirty DN patients with uremia, 28 T2DM patients, and 20 healthy volunteers were enrolled for the determination of CD14(+)CD16(+) fluorescence intensity and TLR4 expression on monocytes by using peripheral blood flow cytometry. |
| 411 | 21847775 | Compared to normal control, T2DM patients and DN uremic patients had a significantly higher CD14(+)CD16(+) fluorescence intensity, TLR4 expression, serum IL-6 and CRP level, whilst these biomarkers were more upregulated in DN uremic patients than in T2DM patients. |
| 412 | 21847775 | Our results suggest that the disturbance in proinflammatory CD14(+)CD16(+) monocytes occurs in T2DM and DN uremic patients. |
| 413 | 21847775 | Such immunological dysfunction may be related to the activation of TLR4/NF-κB and STAT5 signaling pathways underlying the immune abnormalities of CD14(+)CD16(+) monocytes. |
| 414 | 21847775 | Proinflammatory CD14+CD16+ monocytes are associated with microinflammation in patients with type 2 diabetes mellitus and diabetic nephropathy uremia. |
| 415 | 21847775 | In this study, we investigated the expression of Toll-like receptor 4 (TLR4) and CD14(+)CD16(+) monocytes in patients with T2DM and DN patients with uremia and TLR4 response to lipopolysaccharide (LPS), and to further explore the potential effects of inflammatory immune response in T2DM and DN uremia. |
| 416 | 21847775 | Thirty DN patients with uremia, 28 T2DM patients, and 20 healthy volunteers were enrolled for the determination of CD14(+)CD16(+) fluorescence intensity and TLR4 expression on monocytes by using peripheral blood flow cytometry. |
| 417 | 21847775 | Compared to normal control, T2DM patients and DN uremic patients had a significantly higher CD14(+)CD16(+) fluorescence intensity, TLR4 expression, serum IL-6 and CRP level, whilst these biomarkers were more upregulated in DN uremic patients than in T2DM patients. |
| 418 | 21847775 | Our results suggest that the disturbance in proinflammatory CD14(+)CD16(+) monocytes occurs in T2DM and DN uremic patients. |
| 419 | 21847775 | Such immunological dysfunction may be related to the activation of TLR4/NF-κB and STAT5 signaling pathways underlying the immune abnormalities of CD14(+)CD16(+) monocytes. |
| 420 | 21847775 | Proinflammatory CD14+CD16+ monocytes are associated with microinflammation in patients with type 2 diabetes mellitus and diabetic nephropathy uremia. |
| 421 | 21847775 | In this study, we investigated the expression of Toll-like receptor 4 (TLR4) and CD14(+)CD16(+) monocytes in patients with T2DM and DN patients with uremia and TLR4 response to lipopolysaccharide (LPS), and to further explore the potential effects of inflammatory immune response in T2DM and DN uremia. |
| 422 | 21847775 | Thirty DN patients with uremia, 28 T2DM patients, and 20 healthy volunteers were enrolled for the determination of CD14(+)CD16(+) fluorescence intensity and TLR4 expression on monocytes by using peripheral blood flow cytometry. |
| 423 | 21847775 | Compared to normal control, T2DM patients and DN uremic patients had a significantly higher CD14(+)CD16(+) fluorescence intensity, TLR4 expression, serum IL-6 and CRP level, whilst these biomarkers were more upregulated in DN uremic patients than in T2DM patients. |
| 424 | 21847775 | Our results suggest that the disturbance in proinflammatory CD14(+)CD16(+) monocytes occurs in T2DM and DN uremic patients. |
| 425 | 21847775 | Such immunological dysfunction may be related to the activation of TLR4/NF-κB and STAT5 signaling pathways underlying the immune abnormalities of CD14(+)CD16(+) monocytes. |
| 426 | 21847775 | Proinflammatory CD14+CD16+ monocytes are associated with microinflammation in patients with type 2 diabetes mellitus and diabetic nephropathy uremia. |
| 427 | 21847775 | In this study, we investigated the expression of Toll-like receptor 4 (TLR4) and CD14(+)CD16(+) monocytes in patients with T2DM and DN patients with uremia and TLR4 response to lipopolysaccharide (LPS), and to further explore the potential effects of inflammatory immune response in T2DM and DN uremia. |
| 428 | 21847775 | Thirty DN patients with uremia, 28 T2DM patients, and 20 healthy volunteers were enrolled for the determination of CD14(+)CD16(+) fluorescence intensity and TLR4 expression on monocytes by using peripheral blood flow cytometry. |
| 429 | 21847775 | Compared to normal control, T2DM patients and DN uremic patients had a significantly higher CD14(+)CD16(+) fluorescence intensity, TLR4 expression, serum IL-6 and CRP level, whilst these biomarkers were more upregulated in DN uremic patients than in T2DM patients. |
| 430 | 21847775 | Our results suggest that the disturbance in proinflammatory CD14(+)CD16(+) monocytes occurs in T2DM and DN uremic patients. |
| 431 | 21847775 | Such immunological dysfunction may be related to the activation of TLR4/NF-κB and STAT5 signaling pathways underlying the immune abnormalities of CD14(+)CD16(+) monocytes. |
| 432 | 21984919 | Compared with the healthy control mice, diabetic mice had significantly fewer c-kit+ stem cells, and these cells had a lower potency of endothelial differentiation; however, the production of the angiogenic growth factor VEGF did not differ between groups. |
| 433 | 21984919 | A pathway-focused array showed that the c-kit+ stem cells from diabetic mice had up-regulated expression levels of many inflammatory factors, including Tlr4, Cxcl9, Il9, Tgfb1, Il4, and Tnfsf5, but no obvious change in the expression levels of cell cycle molecules. |
| 434 | 21984919 | Interestingly, diabetes-related alterations of the extracellular matrix and adhesion molecules were varied; Pecam, Mmp10, Lamc1, Itgb7, Mmp9, and Timp4 were up-regulated, but Col11a1, Fn1, Admts2, and Itgav were down-regulated. |
| 435 | 22021706 | In this study, we found increased expression of TLR4 but not of TLR2 in the renal tubules of human kidneys with diabetic nephropathy compared with expression of TLR4 and TLR2 in normal kidney and in kidney disease from other causes. |
| 436 | 22021706 | The intensity of tubular TLR4 expression correlated directly with interstitial macrophage infiltration and hemoglobin A1c level and inversely with estimated glomerular filtration rate. |
| 437 | 22021706 | The tubules also upregulated the endogenous TLR4 ligand high-mobility group box 1 in diabetic nephropathy. |
| 438 | 22021706 | In vitro, high glucose induced TLR4 expression via protein kinase C activation in a time- and dose-dependent manner, resulting in upregulation of IL-6 and chemokine (C-C motif) ligand 2 (CCL-2) expression via IκB/NF-κB activation in human proximal tubular epithelial cells. |
| 439 | 22021706 | Silencing of TLR4 with small interfering RNA attenuated high glucose-induced IκB/NF-κB activation, inhibited the downstream synthesis of IL-6 and CCL-2, and impaired the ability of conditioned media from high glucose-treated proximal tubule cells to induce transmigration of mononuclear cells. |
| 440 | 22021706 | Finally, streptozotocin-induced diabetic and uninephrectomized TLR4-deficient mice had significantly less albuminuria, renal dysfunction, renal cortical NF-κB activation, tubular CCL-2 expression, and interstitial macrophage infiltration than wild-type animals. |
| 441 | 22021706 | In this study, we found increased expression of TLR4 but not of TLR2 in the renal tubules of human kidneys with diabetic nephropathy compared with expression of TLR4 and TLR2 in normal kidney and in kidney disease from other causes. |
| 442 | 22021706 | The intensity of tubular TLR4 expression correlated directly with interstitial macrophage infiltration and hemoglobin A1c level and inversely with estimated glomerular filtration rate. |
| 443 | 22021706 | The tubules also upregulated the endogenous TLR4 ligand high-mobility group box 1 in diabetic nephropathy. |
| 444 | 22021706 | In vitro, high glucose induced TLR4 expression via protein kinase C activation in a time- and dose-dependent manner, resulting in upregulation of IL-6 and chemokine (C-C motif) ligand 2 (CCL-2) expression via IκB/NF-κB activation in human proximal tubular epithelial cells. |
| 445 | 22021706 | Silencing of TLR4 with small interfering RNA attenuated high glucose-induced IκB/NF-κB activation, inhibited the downstream synthesis of IL-6 and CCL-2, and impaired the ability of conditioned media from high glucose-treated proximal tubule cells to induce transmigration of mononuclear cells. |
| 446 | 22021706 | Finally, streptozotocin-induced diabetic and uninephrectomized TLR4-deficient mice had significantly less albuminuria, renal dysfunction, renal cortical NF-κB activation, tubular CCL-2 expression, and interstitial macrophage infiltration than wild-type animals. |
| 447 | 22021706 | In this study, we found increased expression of TLR4 but not of TLR2 in the renal tubules of human kidneys with diabetic nephropathy compared with expression of TLR4 and TLR2 in normal kidney and in kidney disease from other causes. |
| 448 | 22021706 | The intensity of tubular TLR4 expression correlated directly with interstitial macrophage infiltration and hemoglobin A1c level and inversely with estimated glomerular filtration rate. |
| 449 | 22021706 | The tubules also upregulated the endogenous TLR4 ligand high-mobility group box 1 in diabetic nephropathy. |
| 450 | 22021706 | In vitro, high glucose induced TLR4 expression via protein kinase C activation in a time- and dose-dependent manner, resulting in upregulation of IL-6 and chemokine (C-C motif) ligand 2 (CCL-2) expression via IκB/NF-κB activation in human proximal tubular epithelial cells. |
| 451 | 22021706 | Silencing of TLR4 with small interfering RNA attenuated high glucose-induced IκB/NF-κB activation, inhibited the downstream synthesis of IL-6 and CCL-2, and impaired the ability of conditioned media from high glucose-treated proximal tubule cells to induce transmigration of mononuclear cells. |
| 452 | 22021706 | Finally, streptozotocin-induced diabetic and uninephrectomized TLR4-deficient mice had significantly less albuminuria, renal dysfunction, renal cortical NF-κB activation, tubular CCL-2 expression, and interstitial macrophage infiltration than wild-type animals. |
| 453 | 22021706 | In this study, we found increased expression of TLR4 but not of TLR2 in the renal tubules of human kidneys with diabetic nephropathy compared with expression of TLR4 and TLR2 in normal kidney and in kidney disease from other causes. |
| 454 | 22021706 | The intensity of tubular TLR4 expression correlated directly with interstitial macrophage infiltration and hemoglobin A1c level and inversely with estimated glomerular filtration rate. |
| 455 | 22021706 | The tubules also upregulated the endogenous TLR4 ligand high-mobility group box 1 in diabetic nephropathy. |
| 456 | 22021706 | In vitro, high glucose induced TLR4 expression via protein kinase C activation in a time- and dose-dependent manner, resulting in upregulation of IL-6 and chemokine (C-C motif) ligand 2 (CCL-2) expression via IκB/NF-κB activation in human proximal tubular epithelial cells. |
| 457 | 22021706 | Silencing of TLR4 with small interfering RNA attenuated high glucose-induced IκB/NF-κB activation, inhibited the downstream synthesis of IL-6 and CCL-2, and impaired the ability of conditioned media from high glucose-treated proximal tubule cells to induce transmigration of mononuclear cells. |
| 458 | 22021706 | Finally, streptozotocin-induced diabetic and uninephrectomized TLR4-deficient mice had significantly less albuminuria, renal dysfunction, renal cortical NF-κB activation, tubular CCL-2 expression, and interstitial macrophage infiltration than wild-type animals. |
| 459 | 22021706 | In this study, we found increased expression of TLR4 but not of TLR2 in the renal tubules of human kidneys with diabetic nephropathy compared with expression of TLR4 and TLR2 in normal kidney and in kidney disease from other causes. |
| 460 | 22021706 | The intensity of tubular TLR4 expression correlated directly with interstitial macrophage infiltration and hemoglobin A1c level and inversely with estimated glomerular filtration rate. |
| 461 | 22021706 | The tubules also upregulated the endogenous TLR4 ligand high-mobility group box 1 in diabetic nephropathy. |
| 462 | 22021706 | In vitro, high glucose induced TLR4 expression via protein kinase C activation in a time- and dose-dependent manner, resulting in upregulation of IL-6 and chemokine (C-C motif) ligand 2 (CCL-2) expression via IκB/NF-κB activation in human proximal tubular epithelial cells. |
| 463 | 22021706 | Silencing of TLR4 with small interfering RNA attenuated high glucose-induced IκB/NF-κB activation, inhibited the downstream synthesis of IL-6 and CCL-2, and impaired the ability of conditioned media from high glucose-treated proximal tubule cells to induce transmigration of mononuclear cells. |
| 464 | 22021706 | Finally, streptozotocin-induced diabetic and uninephrectomized TLR4-deficient mice had significantly less albuminuria, renal dysfunction, renal cortical NF-κB activation, tubular CCL-2 expression, and interstitial macrophage infiltration than wild-type animals. |
| 465 | 22021706 | In this study, we found increased expression of TLR4 but not of TLR2 in the renal tubules of human kidneys with diabetic nephropathy compared with expression of TLR4 and TLR2 in normal kidney and in kidney disease from other causes. |
| 466 | 22021706 | The intensity of tubular TLR4 expression correlated directly with interstitial macrophage infiltration and hemoglobin A1c level and inversely with estimated glomerular filtration rate. |
| 467 | 22021706 | The tubules also upregulated the endogenous TLR4 ligand high-mobility group box 1 in diabetic nephropathy. |
| 468 | 22021706 | In vitro, high glucose induced TLR4 expression via protein kinase C activation in a time- and dose-dependent manner, resulting in upregulation of IL-6 and chemokine (C-C motif) ligand 2 (CCL-2) expression via IκB/NF-κB activation in human proximal tubular epithelial cells. |
| 469 | 22021706 | Silencing of TLR4 with small interfering RNA attenuated high glucose-induced IκB/NF-κB activation, inhibited the downstream synthesis of IL-6 and CCL-2, and impaired the ability of conditioned media from high glucose-treated proximal tubule cells to induce transmigration of mononuclear cells. |
| 470 | 22021706 | Finally, streptozotocin-induced diabetic and uninephrectomized TLR4-deficient mice had significantly less albuminuria, renal dysfunction, renal cortical NF-κB activation, tubular CCL-2 expression, and interstitial macrophage infiltration than wild-type animals. |
| 471 | 22074948 | Mouse resistin modulates adipogenesis and glucose uptake in 3T3-L1 preadipocytes through the ROR1 receptor. |
| 472 | 22074948 | Mouse resistin, a cysteine-rich protein primarily secreted from mature adipocytes, is involved in insulin resistance and type 2 diabetes. |
| 473 | 22074948 | Human resistin, however, is mainly secreted by immune mononuclear cells, and it competes with lipopolysaccharide for the binding to Toll-like receptor 4, which could mediate some of the well-known proinflammatory effects of resistin in humans. |
| 474 | 22074948 | Thus, a recent work identifies an isoform of Decorin (Δ Decorin) as a functional resistin receptor in adipocyte progenitors that may regulate white adipose tissue expansion. |
| 475 | 22074948 | We have demonstrated an interaction of mouse resistin with specific domains of the extracellular region of the ROR1 receptor. |
| 476 | 22074948 | This interaction results in the inhibition of ROR1 phosphorylation, modulates ERK1/2 phosphorylation, and regulates suppressor of cytokine signaling 3, glucose transporter 4, and glucose transporter 1 expression. |
| 477 | 22074948 | Moreover, mouse resistin modulates glucose uptake and promotes adipogenesis of 3T3-L1 cells through ROR1. |
| 478 | 22074948 | In summary, our results identify mouse resistin as a potential inhibitory ligand for the receptor ROR1 and demonstrate, for the first time, that ROR1 plays an important role in adipogenesis and glucose homeostasis in 3T3-L1 cells. |
| 479 | 22074948 | These data open a new line of research that could explain important questions about the resistin mechanism of action in adipogenesis and in the development of insulin resistance. |
| 480 | 22095980 | S100A8 and S100A9 in cardiovascular biology and disease. |
| 481 | 22095980 | There is recent and widespread interest in the damage-associated molecular pattern molecules S100A8 and S100A9 in cardiovascular science. |
| 482 | 22095980 | For example, S100A8 and S100A9 (S100A8/A9) have both intracellular and extracellular actions, they are abundantly expressed in inflammatory and autoimmune states, primarily by myeloid cells but also by other vascular cells, and they modulate inflammatory processes, in part through Toll-like receptor 4 and the receptor for advanced glycation end products. |
| 483 | 22095980 | Furthermore, increased plasma levels of S100A8/A9 predict cardiovascular events in humans, and deletion of these proteins partly protects Apoe(-)(/)(-) mice from atherosclerosis. |
| 484 | 22095980 | Understanding the roles of S100A8 and S100A9 in vascular cell types and the mechanisms whereby these proteins mediate their biological effects may offer new therapeutic strategies to prevent, treat, and predict cardiovascular diseases. |
| 485 | 22253759 | It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS), may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. |
| 486 | 22326531 | Stearoyl-CoA Desaturase 1 (SCD1) is a key factor mediating diabetes in MyD88-deficient mice. |
| 487 | 22326531 | Saturated fatty acids, acting as ligands for toll-like receptor 4 (TLR4), induce inflammation and mediate the development of insulin resistance. |
| 488 | 22326531 | Myeloid differentiation factor 88 (MyD88) is an adaptor protein for TLR4. |
| 489 | 22326531 | In the present study, we found SCD1 was dramatically increased in HFD-fed MyD88-deficient mice liver. |
| 490 | 22326531 | This finding showed the novel linkage between MyD88 and SCD1 in the development of diabetes mellitus. |
| 491 | 22326531 | Stearoyl-CoA Desaturase 1 (SCD1) is a key factor mediating diabetes in MyD88-deficient mice. |
| 492 | 22326531 | Saturated fatty acids, acting as ligands for toll-like receptor 4 (TLR4), induce inflammation and mediate the development of insulin resistance. |
| 493 | 22326531 | Myeloid differentiation factor 88 (MyD88) is an adaptor protein for TLR4. |
| 494 | 22326531 | In the present study, we found SCD1 was dramatically increased in HFD-fed MyD88-deficient mice liver. |
| 495 | 22326531 | This finding showed the novel linkage between MyD88 and SCD1 in the development of diabetes mellitus. |
| 496 | 22367599 | Toll-like receptor (TLR) ligands (TLR2: peptidoglycan, PGN; TLR4: lipopolysaccharide, LPS; TLR5: flagellin, FLG) were used to stimulate alveolar macrophages (AMs), and TNF-α production was measured. |
| 497 | 22367599 | Under hyperglycemic conditions and PGN or FLG stimulation, TNF-α production from AMs was significantly reduced in group B compared with group A. |
| 498 | 22396206 | Here, we show that a Toll-like receptor (TLR) protein, radioprotective 105 (RP105)/myeloid differentiation protein (MD)-1 complex, contributes to high-fat diet (HFD)-induced obesity, adipose tissue inflammation, and insulin resistance. |
| 499 | 22396206 | The RP105/MD-1 complex was expressed by most adipose tissue macrophages (ATMs). |
| 500 | 22396206 | An HFD increased RP105/MD-1 expression on the M1 subset of ATMs that accumulate in eWAT. |
| 501 | 22396206 | RP105 knockout (KO) and MD-1 KO mice had less HFD-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance compared with wild-type (WT) and TLR4 KO mice. |
| 502 | 22396206 | Finally, the saturated fatty acids, palmitic and stearic acids, are endogenous ligands for TLR4, but they did not activate RP105/MD-1. |
| 503 | 22396206 | Thus, the RP105/MD-1 complex is a major mediator of adipose tissue inflammation independent of TLR4 signaling and may represent a novel therapeutic target for obesity-associated metabolic disorders. |
| 504 | 22396206 | Here, we show that a Toll-like receptor (TLR) protein, radioprotective 105 (RP105)/myeloid differentiation protein (MD)-1 complex, contributes to high-fat diet (HFD)-induced obesity, adipose tissue inflammation, and insulin resistance. |
| 505 | 22396206 | The RP105/MD-1 complex was expressed by most adipose tissue macrophages (ATMs). |
| 506 | 22396206 | An HFD increased RP105/MD-1 expression on the M1 subset of ATMs that accumulate in eWAT. |
| 507 | 22396206 | RP105 knockout (KO) and MD-1 KO mice had less HFD-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance compared with wild-type (WT) and TLR4 KO mice. |
| 508 | 22396206 | Finally, the saturated fatty acids, palmitic and stearic acids, are endogenous ligands for TLR4, but they did not activate RP105/MD-1. |
| 509 | 22396206 | Thus, the RP105/MD-1 complex is a major mediator of adipose tissue inflammation independent of TLR4 signaling and may represent a novel therapeutic target for obesity-associated metabolic disorders. |
| 510 | 22396206 | Here, we show that a Toll-like receptor (TLR) protein, radioprotective 105 (RP105)/myeloid differentiation protein (MD)-1 complex, contributes to high-fat diet (HFD)-induced obesity, adipose tissue inflammation, and insulin resistance. |
| 511 | 22396206 | The RP105/MD-1 complex was expressed by most adipose tissue macrophages (ATMs). |
| 512 | 22396206 | An HFD increased RP105/MD-1 expression on the M1 subset of ATMs that accumulate in eWAT. |
| 513 | 22396206 | RP105 knockout (KO) and MD-1 KO mice had less HFD-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance compared with wild-type (WT) and TLR4 KO mice. |
| 514 | 22396206 | Finally, the saturated fatty acids, palmitic and stearic acids, are endogenous ligands for TLR4, but they did not activate RP105/MD-1. |
| 515 | 22396206 | Thus, the RP105/MD-1 complex is a major mediator of adipose tissue inflammation independent of TLR4 signaling and may represent a novel therapeutic target for obesity-associated metabolic disorders. |
| 516 | 22426798 | OBDM patients with or without anemia had higher levels of ferritin and high-sensitivity C-reactive protein than the Cn group. mRNA relative abundance of nuclear factor kappa-light-chain-enhancer of activated B cells was elevated in OBDM with anemia, and mRNA expression of interleukin-6 and toll-like receptor (TLR) 2 was increased in OBDM group in basal high Fe and high glucose concentrations. |
| 517 | 22426798 | The expression of tumor necrosis factor alpha and TLR-4 was increased in OBDM with anemia in all experimental conditions. |
| 518 | 22427667 | The induction of the endoplasmic reticulum resident chaperones, GRP94 and GRP78, by LPS was of a much lower magnitude than the effect of LPS on TLR4 and MD-2 expression. |
| 519 | 22427667 | In face of this apparent insufficiency of chaperone expression, we induced the expression of GRP94 and GRP78 by glucose deprivation. |
| 520 | 22427667 | The inhibition of either GRP94 or GRP78 with siRNA was sufficient to rescue the protective effect of glucose deprivation on LPS-induced endoplasmic reticulum stress. |
| 521 | 22431523 | Retinol-binding protein 4 inhibits insulin signaling in adipocytes by inducing proinflammatory cytokines in macrophages through a c-Jun N-terminal kinase- and toll-like receptor 4-dependent and retinol-independent mechanism. |
| 522 | 22431523 | Serum RBP4 levels correlate highly with insulin resistance, other metabolic syndrome factors, and cardiovascular disease. |
| 523 | 22431523 | Elevated serum RBP4 causes insulin resistance, but the molecular mechanisms are unknown. |
| 524 | 22431523 | Here we show that RBP4 induces expression of proinflammatory cytokines in mouse and human macrophages and thereby indirectly inhibits insulin signaling in cocultured adipocytes. |
| 525 | 22431523 | This occurs through activation of c-Jun N-terminal protein kinase (JNK) and Toll-like receptor 4 (TLR4) pathways independent of the RBP4 receptor, STRA6. |
| 526 | 22431523 | RBP4 effects are markedly attenuated in JNK1-/- JNK2-/- macrophages and TLR4-/- macrophages. |
| 527 | 22431523 | Apo-RBP4 is likely to be physiologically significant since RBP4/retinol ratios are increased in serum of lean and obese insulin-resistant humans compared to ratios in insulin-sensitive humans, indicating that higher apo-RBP4 is associated with insulin resistance independent of obesity. |
| 528 | 22431523 | Thus, RBP4 may cause insulin resistance by contributing to the development of an inflammatory state in adipose tissue through activation of proinflammatory cytokines in macrophages. |
| 529 | 22431523 | This process reveals a novel JNK- and TLR4-dependent and retinol- and STRA6-independent mechanism of action for RBP4. |
| 530 | 22431523 | Retinol-binding protein 4 inhibits insulin signaling in adipocytes by inducing proinflammatory cytokines in macrophages through a c-Jun N-terminal kinase- and toll-like receptor 4-dependent and retinol-independent mechanism. |
| 531 | 22431523 | Serum RBP4 levels correlate highly with insulin resistance, other metabolic syndrome factors, and cardiovascular disease. |
| 532 | 22431523 | Elevated serum RBP4 causes insulin resistance, but the molecular mechanisms are unknown. |
| 533 | 22431523 | Here we show that RBP4 induces expression of proinflammatory cytokines in mouse and human macrophages and thereby indirectly inhibits insulin signaling in cocultured adipocytes. |
| 534 | 22431523 | This occurs through activation of c-Jun N-terminal protein kinase (JNK) and Toll-like receptor 4 (TLR4) pathways independent of the RBP4 receptor, STRA6. |
| 535 | 22431523 | RBP4 effects are markedly attenuated in JNK1-/- JNK2-/- macrophages and TLR4-/- macrophages. |
| 536 | 22431523 | Apo-RBP4 is likely to be physiologically significant since RBP4/retinol ratios are increased in serum of lean and obese insulin-resistant humans compared to ratios in insulin-sensitive humans, indicating that higher apo-RBP4 is associated with insulin resistance independent of obesity. |
| 537 | 22431523 | Thus, RBP4 may cause insulin resistance by contributing to the development of an inflammatory state in adipose tissue through activation of proinflammatory cytokines in macrophages. |
| 538 | 22431523 | This process reveals a novel JNK- and TLR4-dependent and retinol- and STRA6-independent mechanism of action for RBP4. |
| 539 | 22431523 | Retinol-binding protein 4 inhibits insulin signaling in adipocytes by inducing proinflammatory cytokines in macrophages through a c-Jun N-terminal kinase- and toll-like receptor 4-dependent and retinol-independent mechanism. |
| 540 | 22431523 | Serum RBP4 levels correlate highly with insulin resistance, other metabolic syndrome factors, and cardiovascular disease. |
| 541 | 22431523 | Elevated serum RBP4 causes insulin resistance, but the molecular mechanisms are unknown. |
| 542 | 22431523 | Here we show that RBP4 induces expression of proinflammatory cytokines in mouse and human macrophages and thereby indirectly inhibits insulin signaling in cocultured adipocytes. |
| 543 | 22431523 | This occurs through activation of c-Jun N-terminal protein kinase (JNK) and Toll-like receptor 4 (TLR4) pathways independent of the RBP4 receptor, STRA6. |
| 544 | 22431523 | RBP4 effects are markedly attenuated in JNK1-/- JNK2-/- macrophages and TLR4-/- macrophages. |
| 545 | 22431523 | Apo-RBP4 is likely to be physiologically significant since RBP4/retinol ratios are increased in serum of lean and obese insulin-resistant humans compared to ratios in insulin-sensitive humans, indicating that higher apo-RBP4 is associated with insulin resistance independent of obesity. |
| 546 | 22431523 | Thus, RBP4 may cause insulin resistance by contributing to the development of an inflammatory state in adipose tissue through activation of proinflammatory cytokines in macrophages. |
| 547 | 22431523 | This process reveals a novel JNK- and TLR4-dependent and retinol- and STRA6-independent mechanism of action for RBP4. |
| 548 | 22431523 | Retinol-binding protein 4 inhibits insulin signaling in adipocytes by inducing proinflammatory cytokines in macrophages through a c-Jun N-terminal kinase- and toll-like receptor 4-dependent and retinol-independent mechanism. |
| 549 | 22431523 | Serum RBP4 levels correlate highly with insulin resistance, other metabolic syndrome factors, and cardiovascular disease. |
| 550 | 22431523 | Elevated serum RBP4 causes insulin resistance, but the molecular mechanisms are unknown. |
| 551 | 22431523 | Here we show that RBP4 induces expression of proinflammatory cytokines in mouse and human macrophages and thereby indirectly inhibits insulin signaling in cocultured adipocytes. |
| 552 | 22431523 | This occurs through activation of c-Jun N-terminal protein kinase (JNK) and Toll-like receptor 4 (TLR4) pathways independent of the RBP4 receptor, STRA6. |
| 553 | 22431523 | RBP4 effects are markedly attenuated in JNK1-/- JNK2-/- macrophages and TLR4-/- macrophages. |
| 554 | 22431523 | Apo-RBP4 is likely to be physiologically significant since RBP4/retinol ratios are increased in serum of lean and obese insulin-resistant humans compared to ratios in insulin-sensitive humans, indicating that higher apo-RBP4 is associated with insulin resistance independent of obesity. |
| 555 | 22431523 | Thus, RBP4 may cause insulin resistance by contributing to the development of an inflammatory state in adipose tissue through activation of proinflammatory cytokines in macrophages. |
| 556 | 22431523 | This process reveals a novel JNK- and TLR4-dependent and retinol- and STRA6-independent mechanism of action for RBP4. |
| 557 | 22473609 | Oxidative burst, myeloperoxidase (MPO) release, expression of pathogen recognition receptors (TLR2, TLR4, and CD14), and activation markers (CD11b and HLA-DR) were measured on polymorphonuclear (PMN) leukocytes and monocytes. |
| 558 | 22473609 | Concentrations of plasma inflammatory cytokine (interleukin-6 [IL-6], IL-12p70, tumor necrosis factor alpha [TNF-α], monocyte chemoattractant protein 1 [MCP-1], IL-8, IL-1β, and IL-10) were also determined. |
| 559 | 22473609 | Differences were also observed in expression of Toll-like receptor 2 (TLR2), CD14, and CD11b on phagocytes from T2D and ND individuals. |
| 560 | 22473609 | Levels of IL-12p70, MCP-1, and IL-8 were significantly elevated in blood from PC-T2D subjects compared to ND individuals. |
| 561 | 22522614 | Obese rodents were treated by intracerebroventricular injections, with immunoneutralizing antibodies against Toll-like receptor (TLR)4 or tumor necrosis factor (TNF)α, and insulin signal transduction, hepatic steatosis, and gluconeogenesis were evaluated. |
| 562 | 22522614 | The inhibition of either TLR4 or TNFα reduced hypothalamic inflammation, which was accompanied by the reduction of hypothalamic resistance to leptin and improved insulin signal transduction in the liver. |
| 563 | 22645244 | Recently, the LPS receptor, TLR4, has been shown to down-regulate miR-107 in macrophages. |
| 564 | 22645244 | In addition, miR-107 has been demonstrated to be dysregulated in murine and rodent models of obesity and insulin resistance, respectively, with miR-107 contributing to both conditions. |
| 565 | 22645244 | With obesity and inflammation being so intrinsically associated, the link between the miR-107 expression levels, inflammation, and insulin resistance may be of particular importance in metabolic diseases. |
| 566 | 22645244 | The decrease in miR-107 in response to TLR4 may be an attempt to limit insulin resistance, a feature of obesity-related inflammation. |
| 567 | 22645244 | Recently, the LPS receptor, TLR4, has been shown to down-regulate miR-107 in macrophages. |
| 568 | 22645244 | In addition, miR-107 has been demonstrated to be dysregulated in murine and rodent models of obesity and insulin resistance, respectively, with miR-107 contributing to both conditions. |
| 569 | 22645244 | With obesity and inflammation being so intrinsically associated, the link between the miR-107 expression levels, inflammation, and insulin resistance may be of particular importance in metabolic diseases. |
| 570 | 22645244 | The decrease in miR-107 in response to TLR4 may be an attempt to limit insulin resistance, a feature of obesity-related inflammation. |
| 571 | 22734110 | In addition to proteins, a number of diabetic substrates including high glucose per se, advanced glycation end-products and their carbonyl intermediates, angiotensin II, and ultrafiltered growth factors activate a number of signaling pathways including nuclear factor kappa B, protein kinase C, extracellular signal-regulated kinase 1/2, p38, signal transducer and activator of transcription-1 and the generation of reactive oxygen species, to culminate in tubular cell hypertrophy and the accumulation in the interstitium of a repertoire of chemokines, cytokines, growth factors and adhesion molecules capable of orchestrating further inflammation and fibrosis. |
| 572 | 22734110 | On the other hand, there are both in vitro and in vivo data to suggest a role for both TLR2 and TLR4 in DN. |
| 573 | 22842069 | However, by comparison, TLR4-deficient NOD mouse hearts had lower triglyceride accumulation in the early stages of diabetes, which was associated with a reduction in myeloid differentiation primary response gene (88) (MyD88), phosphorylation of p38 MAPK (phospho-p38), lipoprotein lipase (LPL), and JNK levels but increased phospho-AMP-activated protein kinase (AMPK). |
| 574 | 22842069 | TLR4 deficiency in the cells decreased FA-induced augmentation of MyD88, phospho-p38, and LPL, suggesting that TLR4 may modulate FA-induced lipid metabolism in cardiomyocytes. |
| 575 | 22842069 | However, by comparison, TLR4-deficient NOD mouse hearts had lower triglyceride accumulation in the early stages of diabetes, which was associated with a reduction in myeloid differentiation primary response gene (88) (MyD88), phosphorylation of p38 MAPK (phospho-p38), lipoprotein lipase (LPL), and JNK levels but increased phospho-AMP-activated protein kinase (AMPK). |
| 576 | 22842069 | TLR4 deficiency in the cells decreased FA-induced augmentation of MyD88, phospho-p38, and LPL, suggesting that TLR4 may modulate FA-induced lipid metabolism in cardiomyocytes. |
| 577 | 22842477 | Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. |
| 578 | 22842477 | Free fatty acids (FFAs) stimulate adipose tissue inflammation through the TLR4 pathway, resulting in insulin resistance. |
| 579 | 22842477 | Here we show that fetuin-A (FetA) could be this endogenous ligand and that it has a crucial role in regulating insulin sensitivity via Tlr4 signaling in mice. |
| 580 | 22842477 | FetA (officially known as Ahsg) knockdown in mice with insulin resistance caused by a high-fat diet (HFD) resulted in downregulation of Tlr4-mediated inflammatory signaling in adipose tissue, whereas selective administration of FetA induced inflammatory signaling and insulin resistance. |
| 581 | 22842477 | FFA-induced proinflammatory cytokine expression in adipocytes occurred only in the presence of both FetA and Tlr4; removing either of them prevented FFA-induced insulin resistance. |
| 582 | 22842477 | FFAs did not produce insulin resistance in adipocytes with mutated Tlr4 or galactoside-cleaved FetA. |
| 583 | 22842477 | Taken together, our results suggest that FetA fulfills the requirement of an endogenous ligand for TLR4 through which lipids induce insulin resistance. |
| 584 | 22842477 | Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. |
| 585 | 22842477 | Free fatty acids (FFAs) stimulate adipose tissue inflammation through the TLR4 pathway, resulting in insulin resistance. |
| 586 | 22842477 | Here we show that fetuin-A (FetA) could be this endogenous ligand and that it has a crucial role in regulating insulin sensitivity via Tlr4 signaling in mice. |
| 587 | 22842477 | FetA (officially known as Ahsg) knockdown in mice with insulin resistance caused by a high-fat diet (HFD) resulted in downregulation of Tlr4-mediated inflammatory signaling in adipose tissue, whereas selective administration of FetA induced inflammatory signaling and insulin resistance. |
| 588 | 22842477 | FFA-induced proinflammatory cytokine expression in adipocytes occurred only in the presence of both FetA and Tlr4; removing either of them prevented FFA-induced insulin resistance. |
| 589 | 22842477 | FFAs did not produce insulin resistance in adipocytes with mutated Tlr4 or galactoside-cleaved FetA. |
| 590 | 22842477 | Taken together, our results suggest that FetA fulfills the requirement of an endogenous ligand for TLR4 through which lipids induce insulin resistance. |
| 591 | 22842477 | Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. |
| 592 | 22842477 | Free fatty acids (FFAs) stimulate adipose tissue inflammation through the TLR4 pathway, resulting in insulin resistance. |
| 593 | 22842477 | Here we show that fetuin-A (FetA) could be this endogenous ligand and that it has a crucial role in regulating insulin sensitivity via Tlr4 signaling in mice. |
| 594 | 22842477 | FetA (officially known as Ahsg) knockdown in mice with insulin resistance caused by a high-fat diet (HFD) resulted in downregulation of Tlr4-mediated inflammatory signaling in adipose tissue, whereas selective administration of FetA induced inflammatory signaling and insulin resistance. |
| 595 | 22842477 | FFA-induced proinflammatory cytokine expression in adipocytes occurred only in the presence of both FetA and Tlr4; removing either of them prevented FFA-induced insulin resistance. |
| 596 | 22842477 | FFAs did not produce insulin resistance in adipocytes with mutated Tlr4 or galactoside-cleaved FetA. |
| 597 | 22842477 | Taken together, our results suggest that FetA fulfills the requirement of an endogenous ligand for TLR4 through which lipids induce insulin resistance. |
| 598 | 22842477 | Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. |
| 599 | 22842477 | Free fatty acids (FFAs) stimulate adipose tissue inflammation through the TLR4 pathway, resulting in insulin resistance. |
| 600 | 22842477 | Here we show that fetuin-A (FetA) could be this endogenous ligand and that it has a crucial role in regulating insulin sensitivity via Tlr4 signaling in mice. |
| 601 | 22842477 | FetA (officially known as Ahsg) knockdown in mice with insulin resistance caused by a high-fat diet (HFD) resulted in downregulation of Tlr4-mediated inflammatory signaling in adipose tissue, whereas selective administration of FetA induced inflammatory signaling and insulin resistance. |
| 602 | 22842477 | FFA-induced proinflammatory cytokine expression in adipocytes occurred only in the presence of both FetA and Tlr4; removing either of them prevented FFA-induced insulin resistance. |
| 603 | 22842477 | FFAs did not produce insulin resistance in adipocytes with mutated Tlr4 or galactoside-cleaved FetA. |
| 604 | 22842477 | Taken together, our results suggest that FetA fulfills the requirement of an endogenous ligand for TLR4 through which lipids induce insulin resistance. |
| 605 | 22842477 | Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. |
| 606 | 22842477 | Free fatty acids (FFAs) stimulate adipose tissue inflammation through the TLR4 pathway, resulting in insulin resistance. |
| 607 | 22842477 | Here we show that fetuin-A (FetA) could be this endogenous ligand and that it has a crucial role in regulating insulin sensitivity via Tlr4 signaling in mice. |
| 608 | 22842477 | FetA (officially known as Ahsg) knockdown in mice with insulin resistance caused by a high-fat diet (HFD) resulted in downregulation of Tlr4-mediated inflammatory signaling in adipose tissue, whereas selective administration of FetA induced inflammatory signaling and insulin resistance. |
| 609 | 22842477 | FFA-induced proinflammatory cytokine expression in adipocytes occurred only in the presence of both FetA and Tlr4; removing either of them prevented FFA-induced insulin resistance. |
| 610 | 22842477 | FFAs did not produce insulin resistance in adipocytes with mutated Tlr4 or galactoside-cleaved FetA. |
| 611 | 22842477 | Taken together, our results suggest that FetA fulfills the requirement of an endogenous ligand for TLR4 through which lipids induce insulin resistance. |
| 612 | 22842477 | Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. |
| 613 | 22842477 | Free fatty acids (FFAs) stimulate adipose tissue inflammation through the TLR4 pathway, resulting in insulin resistance. |
| 614 | 22842477 | Here we show that fetuin-A (FetA) could be this endogenous ligand and that it has a crucial role in regulating insulin sensitivity via Tlr4 signaling in mice. |
| 615 | 22842477 | FetA (officially known as Ahsg) knockdown in mice with insulin resistance caused by a high-fat diet (HFD) resulted in downregulation of Tlr4-mediated inflammatory signaling in adipose tissue, whereas selective administration of FetA induced inflammatory signaling and insulin resistance. |
| 616 | 22842477 | FFA-induced proinflammatory cytokine expression in adipocytes occurred only in the presence of both FetA and Tlr4; removing either of them prevented FFA-induced insulin resistance. |
| 617 | 22842477 | FFAs did not produce insulin resistance in adipocytes with mutated Tlr4 or galactoside-cleaved FetA. |
| 618 | 22842477 | Taken together, our results suggest that FetA fulfills the requirement of an endogenous ligand for TLR4 through which lipids induce insulin resistance. |
| 619 | 22845335 | It has been suggested that HMGB-1 itself can signal through RAGEs (receptor for advanced glycation end products) and through the Toll-Like Receptors TLR2 and TLR4. |
| 620 | 22851489 | Increased tenascin C and Toll-like receptor 4 levels in visceral adipose tissue as a link between inflammation and extracellular matrix remodeling in obesity. |
| 621 | 22874765 | Thus we evaluated the effect of high glucose on TLR2 and TLR4 expression in mouse mesangial cells (MMC) in vitro. |
| 622 | 22874765 | Furthermore, expression of a TLR4 downstream signaling cascade including myeloid differentiation factor 88 (MyD88), interferon regulatory factor 3 (IRF3), and Toll interleukin receptor domain containing adaptor inducing interferon-β (TRIF)-related adaptor molecule (TRAM) were significantly increased in cells exposed to 25 mM glucose (P < 0.05). |
| 623 | 22874765 | There was also a significant increase in NF-κB activation along with increased secretion of inflammatory cytokines IL-6 and monocyte chemotactic protein-1. |
| 624 | 22874765 | Thus we evaluated the effect of high glucose on TLR2 and TLR4 expression in mouse mesangial cells (MMC) in vitro. |
| 625 | 22874765 | Furthermore, expression of a TLR4 downstream signaling cascade including myeloid differentiation factor 88 (MyD88), interferon regulatory factor 3 (IRF3), and Toll interleukin receptor domain containing adaptor inducing interferon-β (TRIF)-related adaptor molecule (TRAM) were significantly increased in cells exposed to 25 mM glucose (P < 0.05). |
| 626 | 22874765 | There was also a significant increase in NF-κB activation along with increased secretion of inflammatory cytokines IL-6 and monocyte chemotactic protein-1. |
| 627 | 22910613 | The protein levels of TNF-α and IL-1β, two downstream proinflammatory cytokines of TLR4 signaling pathway, were also significantly raised and correlated with mechanical/thermal hypersensitivity in diabetic rats. |
| 628 | 22961082 | Central resistin overexposure induces insulin resistance through Toll-like receptor 4. |
| 629 | 22961082 | Resistin promotes both inflammation and insulin resistance associated with energy homeostasis impairment. |
| 630 | 22961082 | However, the resistin receptor and the molecular mechanisms mediating its effects in the hypothalamus, crucial for energy homeostasis control, and key insulin-sensitive tissues are still unknown. |
| 631 | 22961082 | In the current study, we report that chronic resistin infusion in the lateral cerebral ventricle of normal rats markedly affects both hypothalamic and peripheral insulin responsiveness. |
| 632 | 22961082 | Central resistin treatment inhibited insulin-dependent phosphorylation of insulin receptor (IR), AKT, and extracellular signal-related kinase 1/2 associated with reduced IR expression and with upregulation of suppressor of cytokine signaling-3 and phosphotyrosine phosphatase 1B, two negative regulators of insulin signaling. |
| 633 | 22961082 | Additionally, central resistin promotes the activation of the serine kinases Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase, enhances the serine phosphorylation of insulin receptor substrate-1, and increases the expression of the proinflammatory cytokine interleukin-6 in the hypothalamus and key peripheral insulin-sensitive tissues. |
| 634 | 22961082 | Taken together, our findings clearly identify TLR4 as the binding site for resistin in the hypothalamus and bring new insight into the molecular mechanisms involved in resistin-induced inflammation and insulin resistance in the whole animal. |
| 635 | 22961082 | Central resistin overexposure induces insulin resistance through Toll-like receptor 4. |
| 636 | 22961082 | Resistin promotes both inflammation and insulin resistance associated with energy homeostasis impairment. |
| 637 | 22961082 | However, the resistin receptor and the molecular mechanisms mediating its effects in the hypothalamus, crucial for energy homeostasis control, and key insulin-sensitive tissues are still unknown. |
| 638 | 22961082 | In the current study, we report that chronic resistin infusion in the lateral cerebral ventricle of normal rats markedly affects both hypothalamic and peripheral insulin responsiveness. |
| 639 | 22961082 | Central resistin treatment inhibited insulin-dependent phosphorylation of insulin receptor (IR), AKT, and extracellular signal-related kinase 1/2 associated with reduced IR expression and with upregulation of suppressor of cytokine signaling-3 and phosphotyrosine phosphatase 1B, two negative regulators of insulin signaling. |
| 640 | 22961082 | Additionally, central resistin promotes the activation of the serine kinases Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase, enhances the serine phosphorylation of insulin receptor substrate-1, and increases the expression of the proinflammatory cytokine interleukin-6 in the hypothalamus and key peripheral insulin-sensitive tissues. |
| 641 | 22961082 | Taken together, our findings clearly identify TLR4 as the binding site for resistin in the hypothalamus and bring new insight into the molecular mechanisms involved in resistin-induced inflammation and insulin resistance in the whole animal. |
| 642 | 23011593 | Receptor for advanced glycation end products regulates adipocyte hypertrophy and insulin sensitivity in mice: involvement of Toll-like receptor 2. |
| 643 | 23011593 | Furthermore, double knockdown of high mobility group box-1 and S100b, both of which are RAGE ligands endogenously expressed in 3T3-L1 cells, also canceled RAGE-medicated adipocyte hypertrophy, implicating a fundamental role of ligands-RAGE ligation. |
| 644 | 23011593 | Adipocyte hypertrophy induced by RAGE overexpression is associated with suppression of glucose transporter type 4 and adiponectin mRNA expression, attenuated insulin-stimulated glucose uptake, and insulin-stimulated signaling. |
| 645 | 23011593 | Toll-like receptor (Tlr)2 mRNA, but not Tlr4 mRNA, is rapidly upregulated by RAGE overexpression, and inhibition of Tlr2 almost completely abrogates RAGE-mediated adipocyte hypertrophy. |
| 646 | 23011593 | Finally, RAGE(-/-) mice exhibited significantly less body weight, epididymal fat weight, epididymal adipocyte size, higher serum adiponectin levels, and higher insulin sensitivity than wild-type mice. |
| 647 | 23011593 | Thus, RAGE appears to be involved in mouse adipocyte hypertrophy and insulin sensitivity, whereas Tlr2 regulation may partly play a role. |
| 648 | 23015294 | LBP aids in lipopolysaccharide binding to Toll-like receptor-4. miR883b-5p blockade also abolished the protective effects of ApN on proinflammatory adipokine induction. |
| 649 | 23015294 | We identified several novel miRNAs that are regulated by ApN in AT in vivo. miR883b-5p, which is up-regulated by ApN represses LBP and Toll-like receptor-4 signaling, acting therefore as a major mediator of the antiinflammatory action of ApN. |
| 650 | 23015294 | LBP aids in lipopolysaccharide binding to Toll-like receptor-4. miR883b-5p blockade also abolished the protective effects of ApN on proinflammatory adipokine induction. |
| 651 | 23015294 | We identified several novel miRNAs that are regulated by ApN in AT in vivo. miR883b-5p, which is up-regulated by ApN represses LBP and Toll-like receptor-4 signaling, acting therefore as a major mediator of the antiinflammatory action of ApN. |
| 652 | 23041150 | We used reverse transcription polymerase chain reaction and western blotting to determine the expression of Toll-like receptor 4 (TLR4), matrix metalloproteinase-2 (MMP-2) and NF-κB p65 in MSCs under high glucose (HG) with or without pretreatment with AS-IV. |
| 653 | 23041150 | The surface expression of TLR4 was checked by flow cytometry and the expression of TNF-α and MCP-1 were detected by ELISA in diabetes patients treated with AS-IV. |
| 654 | 23041150 | AS-IV decreased the TLR4, TNF-α and MCP-1 expression in patients. |
| 655 | 23041150 | We used reverse transcription polymerase chain reaction and western blotting to determine the expression of Toll-like receptor 4 (TLR4), matrix metalloproteinase-2 (MMP-2) and NF-κB p65 in MSCs under high glucose (HG) with or without pretreatment with AS-IV. |
| 656 | 23041150 | The surface expression of TLR4 was checked by flow cytometry and the expression of TNF-α and MCP-1 were detected by ELISA in diabetes patients treated with AS-IV. |
| 657 | 23041150 | AS-IV decreased the TLR4, TNF-α and MCP-1 expression in patients. |
| 658 | 23041150 | We used reverse transcription polymerase chain reaction and western blotting to determine the expression of Toll-like receptor 4 (TLR4), matrix metalloproteinase-2 (MMP-2) and NF-κB p65 in MSCs under high glucose (HG) with or without pretreatment with AS-IV. |
| 659 | 23041150 | The surface expression of TLR4 was checked by flow cytometry and the expression of TNF-α and MCP-1 were detected by ELISA in diabetes patients treated with AS-IV. |
| 660 | 23041150 | AS-IV decreased the TLR4, TNF-α and MCP-1 expression in patients. |
| 661 | 23060524 | TLR4 antagonist reduces early-stage atherosclerosis in diabetic apolipoprotein E-deficient mice. |
| 662 | 23060524 | In this study, we determined the effect of Rhodobacter sphaeroides lipopolysaccharide (Rs-LPS), an established TLR4 antagonist, on early-stage atherosclerosis in nondiabetic and streptozotocin-induced diabetic apolipoprotein E-deficient (Apoe(-/-)) mice. |
| 663 | 23060524 | Furthermore, immunohistochemistry studies showed that Rs-LPS inhibited the expression of interleukin 6 and matrix metalloproteinase-9 and reduced the content of monocytes and macrophages in atherosclerotic plaques. |
| 664 | 23060524 | Taken together, this study demonstrated for the first time that TLR4 antagonist inhibited vascular inflammation and atherogenesis in diabetic Apoe(-/-) mice and lowered serum cholesterol and triglyceride levels in nondiabetic Apoe(-/-) mice. |
| 665 | 23060524 | TLR4 antagonist reduces early-stage atherosclerosis in diabetic apolipoprotein E-deficient mice. |
| 666 | 23060524 | In this study, we determined the effect of Rhodobacter sphaeroides lipopolysaccharide (Rs-LPS), an established TLR4 antagonist, on early-stage atherosclerosis in nondiabetic and streptozotocin-induced diabetic apolipoprotein E-deficient (Apoe(-/-)) mice. |
| 667 | 23060524 | Furthermore, immunohistochemistry studies showed that Rs-LPS inhibited the expression of interleukin 6 and matrix metalloproteinase-9 and reduced the content of monocytes and macrophages in atherosclerotic plaques. |
| 668 | 23060524 | Taken together, this study demonstrated for the first time that TLR4 antagonist inhibited vascular inflammation and atherogenesis in diabetic Apoe(-/-) mice and lowered serum cholesterol and triglyceride levels in nondiabetic Apoe(-/-) mice. |
| 669 | 23060524 | TLR4 antagonist reduces early-stage atherosclerosis in diabetic apolipoprotein E-deficient mice. |
| 670 | 23060524 | In this study, we determined the effect of Rhodobacter sphaeroides lipopolysaccharide (Rs-LPS), an established TLR4 antagonist, on early-stage atherosclerosis in nondiabetic and streptozotocin-induced diabetic apolipoprotein E-deficient (Apoe(-/-)) mice. |
| 671 | 23060524 | Furthermore, immunohistochemistry studies showed that Rs-LPS inhibited the expression of interleukin 6 and matrix metalloproteinase-9 and reduced the content of monocytes and macrophages in atherosclerotic plaques. |
| 672 | 23060524 | Taken together, this study demonstrated for the first time that TLR4 antagonist inhibited vascular inflammation and atherogenesis in diabetic Apoe(-/-) mice and lowered serum cholesterol and triglyceride levels in nondiabetic Apoe(-/-) mice. |
| 673 | 23091345 | In the study, we genotyped TLRs gene polymorphisms, including TLR2 Arg677Trp and Arg753Gln, TLR4 Asp299Gly and Thr399Ile, TLR9-1486T/C and -1237T/C. |
| 674 | 23091345 | In addition, we were surprised to find that the commonly reported TLR SNPs in the Western countries, like TLR2 Arg677Trp or Arg753Gln, TLR4 Asp299Gly or Thr399Ile and TLR9-1237T/C, were not polymorphic at all in all study subjects. |
| 675 | 23091345 | In conclusion, our data suggests that TLR2 Arg677Trp or Arg753Gln, TLR4 Asp299Gly or Thr399Ile and TLR9-1237T/C polymorphisms have low frequency and TLR9-1486T/C polymorphism may not be a suitable marker in predicting the susceptibility to type 2 diabetes or coronary artery disease in the Chinese Han population. |
| 676 | 23091345 | In the study, we genotyped TLRs gene polymorphisms, including TLR2 Arg677Trp and Arg753Gln, TLR4 Asp299Gly and Thr399Ile, TLR9-1486T/C and -1237T/C. |
| 677 | 23091345 | In addition, we were surprised to find that the commonly reported TLR SNPs in the Western countries, like TLR2 Arg677Trp or Arg753Gln, TLR4 Asp299Gly or Thr399Ile and TLR9-1237T/C, were not polymorphic at all in all study subjects. |
| 678 | 23091345 | In conclusion, our data suggests that TLR2 Arg677Trp or Arg753Gln, TLR4 Asp299Gly or Thr399Ile and TLR9-1237T/C polymorphisms have low frequency and TLR9-1486T/C polymorphism may not be a suitable marker in predicting the susceptibility to type 2 diabetes or coronary artery disease in the Chinese Han population. |
| 679 | 23091345 | In the study, we genotyped TLRs gene polymorphisms, including TLR2 Arg677Trp and Arg753Gln, TLR4 Asp299Gly and Thr399Ile, TLR9-1486T/C and -1237T/C. |
| 680 | 23091345 | In addition, we were surprised to find that the commonly reported TLR SNPs in the Western countries, like TLR2 Arg677Trp or Arg753Gln, TLR4 Asp299Gly or Thr399Ile and TLR9-1237T/C, were not polymorphic at all in all study subjects. |
| 681 | 23091345 | In conclusion, our data suggests that TLR2 Arg677Trp or Arg753Gln, TLR4 Asp299Gly or Thr399Ile and TLR9-1237T/C polymorphisms have low frequency and TLR9-1486T/C polymorphism may not be a suitable marker in predicting the susceptibility to type 2 diabetes or coronary artery disease in the Chinese Han population. |
| 682 | 23235477 | Unexpectedly, while Toll-like receptor 4 (TLR4) expression levels were comparable in kidneys of CHOP(-/-) and wild-type (WT) mice, CHOP(-/-) mice developed more severe AKI after LPS injection. |
| 683 | 23235477 | Additionally, the kidneys of LPS-treated CHOP(-/-) mice had a more prominent increase in NF-κB activation and further upregulation of proinflammatory genes, i.e., c-x-c motif ligand 1 (CXCL-1), macrophage inflammatory protein-2 (MIP-2), and IL-6. |
| 684 | 23251812 | Octanoylated Ghrelin Inhibits the Activation of the Palmitic Acid-Induced TLR4/NF-κB Signaling Pathway in THP-1 Macrophages. |
| 685 | 23251812 | To investigate the effect of acylated ghrelin on the activation of TLR4/NF-κB signaling pathway induced by palmitic acid in human monocyte-derived (THP-1) macrophages, THP-1 macrophages were cultured for 12 h by palmitic acid with various concentrations. |
| 686 | 23251812 | We observed the level of TLR4, NF-κB p65 phosphorylation in THP-1 macrophages and TNF-α, IL-1β in culture supernatant. |
| 687 | 23251812 | TLR4 protein and NF-κB p65 phosphorylation was measured by western blotting. |
| 688 | 23251812 | Compared to the THP-1 macrophages without palmitic acid, the level of TLR4 mRNA protein and NF-κB p65 phosphorylation and the expression of TNF-α and IL-1β increased after treatment by palmitic acid in a dose-dependent fashion (P < 0.05). |
| 689 | 23251812 | So, we make a conclusion that acylated ghrelin can regulate the activation of TLR4/NF-κB signaling pathway and inhibit the release of inflammatory cytokines in THP-1 macrophages which are stimulated by palmitic acid in a dose-dependent fashion. |
| 690 | 23251812 | Octanoylated Ghrelin Inhibits the Activation of the Palmitic Acid-Induced TLR4/NF-κB Signaling Pathway in THP-1 Macrophages. |
| 691 | 23251812 | To investigate the effect of acylated ghrelin on the activation of TLR4/NF-κB signaling pathway induced by palmitic acid in human monocyte-derived (THP-1) macrophages, THP-1 macrophages were cultured for 12 h by palmitic acid with various concentrations. |
| 692 | 23251812 | We observed the level of TLR4, NF-κB p65 phosphorylation in THP-1 macrophages and TNF-α, IL-1β in culture supernatant. |
| 693 | 23251812 | TLR4 protein and NF-κB p65 phosphorylation was measured by western blotting. |
| 694 | 23251812 | Compared to the THP-1 macrophages without palmitic acid, the level of TLR4 mRNA protein and NF-κB p65 phosphorylation and the expression of TNF-α and IL-1β increased after treatment by palmitic acid in a dose-dependent fashion (P < 0.05). |
| 695 | 23251812 | So, we make a conclusion that acylated ghrelin can regulate the activation of TLR4/NF-κB signaling pathway and inhibit the release of inflammatory cytokines in THP-1 macrophages which are stimulated by palmitic acid in a dose-dependent fashion. |
| 696 | 23251812 | Octanoylated Ghrelin Inhibits the Activation of the Palmitic Acid-Induced TLR4/NF-κB Signaling Pathway in THP-1 Macrophages. |
| 697 | 23251812 | To investigate the effect of acylated ghrelin on the activation of TLR4/NF-κB signaling pathway induced by palmitic acid in human monocyte-derived (THP-1) macrophages, THP-1 macrophages were cultured for 12 h by palmitic acid with various concentrations. |
| 698 | 23251812 | We observed the level of TLR4, NF-κB p65 phosphorylation in THP-1 macrophages and TNF-α, IL-1β in culture supernatant. |
| 699 | 23251812 | TLR4 protein and NF-κB p65 phosphorylation was measured by western blotting. |
| 700 | 23251812 | Compared to the THP-1 macrophages without palmitic acid, the level of TLR4 mRNA protein and NF-κB p65 phosphorylation and the expression of TNF-α and IL-1β increased after treatment by palmitic acid in a dose-dependent fashion (P < 0.05). |
| 701 | 23251812 | So, we make a conclusion that acylated ghrelin can regulate the activation of TLR4/NF-κB signaling pathway and inhibit the release of inflammatory cytokines in THP-1 macrophages which are stimulated by palmitic acid in a dose-dependent fashion. |
| 702 | 23251812 | Octanoylated Ghrelin Inhibits the Activation of the Palmitic Acid-Induced TLR4/NF-κB Signaling Pathway in THP-1 Macrophages. |
| 703 | 23251812 | To investigate the effect of acylated ghrelin on the activation of TLR4/NF-κB signaling pathway induced by palmitic acid in human monocyte-derived (THP-1) macrophages, THP-1 macrophages were cultured for 12 h by palmitic acid with various concentrations. |
| 704 | 23251812 | We observed the level of TLR4, NF-κB p65 phosphorylation in THP-1 macrophages and TNF-α, IL-1β in culture supernatant. |
| 705 | 23251812 | TLR4 protein and NF-κB p65 phosphorylation was measured by western blotting. |
| 706 | 23251812 | Compared to the THP-1 macrophages without palmitic acid, the level of TLR4 mRNA protein and NF-κB p65 phosphorylation and the expression of TNF-α and IL-1β increased after treatment by palmitic acid in a dose-dependent fashion (P < 0.05). |
| 707 | 23251812 | So, we make a conclusion that acylated ghrelin can regulate the activation of TLR4/NF-κB signaling pathway and inhibit the release of inflammatory cytokines in THP-1 macrophages which are stimulated by palmitic acid in a dose-dependent fashion. |
| 708 | 23251812 | Octanoylated Ghrelin Inhibits the Activation of the Palmitic Acid-Induced TLR4/NF-κB Signaling Pathway in THP-1 Macrophages. |
| 709 | 23251812 | To investigate the effect of acylated ghrelin on the activation of TLR4/NF-κB signaling pathway induced by palmitic acid in human monocyte-derived (THP-1) macrophages, THP-1 macrophages were cultured for 12 h by palmitic acid with various concentrations. |
| 710 | 23251812 | We observed the level of TLR4, NF-κB p65 phosphorylation in THP-1 macrophages and TNF-α, IL-1β in culture supernatant. |
| 711 | 23251812 | TLR4 protein and NF-κB p65 phosphorylation was measured by western blotting. |
| 712 | 23251812 | Compared to the THP-1 macrophages without palmitic acid, the level of TLR4 mRNA protein and NF-κB p65 phosphorylation and the expression of TNF-α and IL-1β increased after treatment by palmitic acid in a dose-dependent fashion (P < 0.05). |
| 713 | 23251812 | So, we make a conclusion that acylated ghrelin can regulate the activation of TLR4/NF-κB signaling pathway and inhibit the release of inflammatory cytokines in THP-1 macrophages which are stimulated by palmitic acid in a dose-dependent fashion. |
| 714 | 23251812 | Octanoylated Ghrelin Inhibits the Activation of the Palmitic Acid-Induced TLR4/NF-κB Signaling Pathway in THP-1 Macrophages. |
| 715 | 23251812 | To investigate the effect of acylated ghrelin on the activation of TLR4/NF-κB signaling pathway induced by palmitic acid in human monocyte-derived (THP-1) macrophages, THP-1 macrophages were cultured for 12 h by palmitic acid with various concentrations. |
| 716 | 23251812 | We observed the level of TLR4, NF-κB p65 phosphorylation in THP-1 macrophages and TNF-α, IL-1β in culture supernatant. |
| 717 | 23251812 | TLR4 protein and NF-κB p65 phosphorylation was measured by western blotting. |
| 718 | 23251812 | Compared to the THP-1 macrophages without palmitic acid, the level of TLR4 mRNA protein and NF-κB p65 phosphorylation and the expression of TNF-α and IL-1β increased after treatment by palmitic acid in a dose-dependent fashion (P < 0.05). |
| 719 | 23251812 | So, we make a conclusion that acylated ghrelin can regulate the activation of TLR4/NF-κB signaling pathway and inhibit the release of inflammatory cytokines in THP-1 macrophages which are stimulated by palmitic acid in a dose-dependent fashion. |
| 720 | 23326455 | The levels of fasting blood glucose, serum insulin and glucose tolerance were measured and the relative levels of insulin-related phosphatidylinositol 3-kinase (PI3K)/Akt, insulin receptor (IR) and IR substrate 1 (IRS1) phosphorylation were determined. |
| 721 | 23326455 | The levels of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6- phosphatase (G6Pase), toll like receptor 4 (TLR4), tumor necrosis factor (TNF)-α and IL-6 expression and nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK) and p38 MAPK activation in the liver were examined. |
| 722 | 23326455 | EPO treatment significantly reduced the body weights and the levels of fasting blood glucose and serum insulin and improved the HFD-induced glucose intolerance in mice. |
| 723 | 23326455 | EPO treatment significantly enhanced the levels of Akt, but not IR and IRS1, phosphorylation, accompanied by inhibiting the PEPCK and G6Pase expression in the liver. |
| 724 | 23326455 | Furthermore, EPO treatment mitigated the HFD-induced inflammatory TNF-α and IL-6 production, TLR4 expression, NF-κB and JNK, but not ERK and p38 MAPK, phosphorylation in the liver. |
| 725 | 23326455 | The levels of fasting blood glucose, serum insulin and glucose tolerance were measured and the relative levels of insulin-related phosphatidylinositol 3-kinase (PI3K)/Akt, insulin receptor (IR) and IR substrate 1 (IRS1) phosphorylation were determined. |
| 726 | 23326455 | The levels of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6- phosphatase (G6Pase), toll like receptor 4 (TLR4), tumor necrosis factor (TNF)-α and IL-6 expression and nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK) and p38 MAPK activation in the liver were examined. |
| 727 | 23326455 | EPO treatment significantly reduced the body weights and the levels of fasting blood glucose and serum insulin and improved the HFD-induced glucose intolerance in mice. |
| 728 | 23326455 | EPO treatment significantly enhanced the levels of Akt, but not IR and IRS1, phosphorylation, accompanied by inhibiting the PEPCK and G6Pase expression in the liver. |
| 729 | 23326455 | Furthermore, EPO treatment mitigated the HFD-induced inflammatory TNF-α and IL-6 production, TLR4 expression, NF-κB and JNK, but not ERK and p38 MAPK, phosphorylation in the liver. |
| 730 | 23333931 | 25-Hydroxyvitamin D3 attenuates experimental periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in diabetic mice. |
| 731 | 23333931 | Immunohistochemical staining and western blot analysis of gingival epithelia revealed that vitamin D receptor (VDR) expression was enhanced upon 25-OHD3 treatment, while toll-like receptor 4 (TLR4) expression was reduced. |
| 732 | 23333931 | The expressions of Janus family kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3 as well as their phosphorylation were inhibited in gingival epithelia of diabetic periodontitis mice, whereas the expression and phosphorylation of STAT1 remained unchanged. |
| 733 | 23333931 | These results suggest that 25-OHD3 could improve diabetic periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in the gingival epithelium. |
| 734 | 23333931 | 25-Hydroxyvitamin D3 attenuates experimental periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in diabetic mice. |
| 735 | 23333931 | Immunohistochemical staining and western blot analysis of gingival epithelia revealed that vitamin D receptor (VDR) expression was enhanced upon 25-OHD3 treatment, while toll-like receptor 4 (TLR4) expression was reduced. |
| 736 | 23333931 | The expressions of Janus family kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3 as well as their phosphorylation were inhibited in gingival epithelia of diabetic periodontitis mice, whereas the expression and phosphorylation of STAT1 remained unchanged. |
| 737 | 23333931 | These results suggest that 25-OHD3 could improve diabetic periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in the gingival epithelium. |
| 738 | 23333931 | 25-Hydroxyvitamin D3 attenuates experimental periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in diabetic mice. |
| 739 | 23333931 | Immunohistochemical staining and western blot analysis of gingival epithelia revealed that vitamin D receptor (VDR) expression was enhanced upon 25-OHD3 treatment, while toll-like receptor 4 (TLR4) expression was reduced. |
| 740 | 23333931 | The expressions of Janus family kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3 as well as their phosphorylation were inhibited in gingival epithelia of diabetic periodontitis mice, whereas the expression and phosphorylation of STAT1 remained unchanged. |
| 741 | 23333931 | These results suggest that 25-OHD3 could improve diabetic periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in the gingival epithelium. |
| 742 | 23349502 | Cbl-b is a critical regulator of macrophage activation associated with obesity-induced insulin resistance in mice. |
| 743 | 23349502 | We previously reported the potential involvement of casitas B-cell lymphoma-b (Cbl-b) in aging-related murine insulin resistance. |
| 744 | 23349502 | Because obesity also induces macrophage recruitment into adipose tissue, we elucidated here the role of Cbl-b in obesity-related insulin resistance. |
| 745 | 23349502 | Cbl-b(+/+) and Cbl-b(-/-) mice were fed a high-fat diet (HFD) and then examined for obesity-related changes in insulin signaling. |
| 746 | 23349502 | In macrophages, Cbl-b suppressed saturated FA-induced Toll-like receptor 4 (TLR4) signaling by ubiquitination and degradation of TLR4. |
| 747 | 23349502 | The physiological role of Cbl-b in vivo was also examined by bone marrow transplantation and Eritoran, a TLR4 antagonist. |
| 748 | 23349502 | Hematopoietic cell-specific depletion of the Cbl-b gene induced disturbed responses on insulin and glucose tolerance tests. |
| 749 | 23349502 | Blockade of TLR4 signaling by Eritoran reduced fasting blood glucose and serum interleukin-6 levels in obese Cbl-b(-/-) mice. |
| 750 | 23349502 | These results suggest that Cbl-b deficiency could exaggerate HFD-induced insulin resistance through saturated FA-mediated macrophage activation. |
| 751 | 23349502 | Therefore, inhibition of TLR4 signaling is an attractive therapeutic strategy for treatment of obesity-related insulin resistance. |
| 752 | 23349502 | Cbl-b is a critical regulator of macrophage activation associated with obesity-induced insulin resistance in mice. |
| 753 | 23349502 | We previously reported the potential involvement of casitas B-cell lymphoma-b (Cbl-b) in aging-related murine insulin resistance. |
| 754 | 23349502 | Because obesity also induces macrophage recruitment into adipose tissue, we elucidated here the role of Cbl-b in obesity-related insulin resistance. |
| 755 | 23349502 | Cbl-b(+/+) and Cbl-b(-/-) mice were fed a high-fat diet (HFD) and then examined for obesity-related changes in insulin signaling. |
| 756 | 23349502 | In macrophages, Cbl-b suppressed saturated FA-induced Toll-like receptor 4 (TLR4) signaling by ubiquitination and degradation of TLR4. |
| 757 | 23349502 | The physiological role of Cbl-b in vivo was also examined by bone marrow transplantation and Eritoran, a TLR4 antagonist. |
| 758 | 23349502 | Hematopoietic cell-specific depletion of the Cbl-b gene induced disturbed responses on insulin and glucose tolerance tests. |
| 759 | 23349502 | Blockade of TLR4 signaling by Eritoran reduced fasting blood glucose and serum interleukin-6 levels in obese Cbl-b(-/-) mice. |
| 760 | 23349502 | These results suggest that Cbl-b deficiency could exaggerate HFD-induced insulin resistance through saturated FA-mediated macrophage activation. |
| 761 | 23349502 | Therefore, inhibition of TLR4 signaling is an attractive therapeutic strategy for treatment of obesity-related insulin resistance. |
| 762 | 23349502 | Cbl-b is a critical regulator of macrophage activation associated with obesity-induced insulin resistance in mice. |
| 763 | 23349502 | We previously reported the potential involvement of casitas B-cell lymphoma-b (Cbl-b) in aging-related murine insulin resistance. |
| 764 | 23349502 | Because obesity also induces macrophage recruitment into adipose tissue, we elucidated here the role of Cbl-b in obesity-related insulin resistance. |
| 765 | 23349502 | Cbl-b(+/+) and Cbl-b(-/-) mice were fed a high-fat diet (HFD) and then examined for obesity-related changes in insulin signaling. |
| 766 | 23349502 | In macrophages, Cbl-b suppressed saturated FA-induced Toll-like receptor 4 (TLR4) signaling by ubiquitination and degradation of TLR4. |
| 767 | 23349502 | The physiological role of Cbl-b in vivo was also examined by bone marrow transplantation and Eritoran, a TLR4 antagonist. |
| 768 | 23349502 | Hematopoietic cell-specific depletion of the Cbl-b gene induced disturbed responses on insulin and glucose tolerance tests. |
| 769 | 23349502 | Blockade of TLR4 signaling by Eritoran reduced fasting blood glucose and serum interleukin-6 levels in obese Cbl-b(-/-) mice. |
| 770 | 23349502 | These results suggest that Cbl-b deficiency could exaggerate HFD-induced insulin resistance through saturated FA-mediated macrophage activation. |
| 771 | 23349502 | Therefore, inhibition of TLR4 signaling is an attractive therapeutic strategy for treatment of obesity-related insulin resistance. |
| 772 | 23349502 | Cbl-b is a critical regulator of macrophage activation associated with obesity-induced insulin resistance in mice. |
| 773 | 23349502 | We previously reported the potential involvement of casitas B-cell lymphoma-b (Cbl-b) in aging-related murine insulin resistance. |
| 774 | 23349502 | Because obesity also induces macrophage recruitment into adipose tissue, we elucidated here the role of Cbl-b in obesity-related insulin resistance. |
| 775 | 23349502 | Cbl-b(+/+) and Cbl-b(-/-) mice were fed a high-fat diet (HFD) and then examined for obesity-related changes in insulin signaling. |
| 776 | 23349502 | In macrophages, Cbl-b suppressed saturated FA-induced Toll-like receptor 4 (TLR4) signaling by ubiquitination and degradation of TLR4. |
| 777 | 23349502 | The physiological role of Cbl-b in vivo was also examined by bone marrow transplantation and Eritoran, a TLR4 antagonist. |
| 778 | 23349502 | Hematopoietic cell-specific depletion of the Cbl-b gene induced disturbed responses on insulin and glucose tolerance tests. |
| 779 | 23349502 | Blockade of TLR4 signaling by Eritoran reduced fasting blood glucose and serum interleukin-6 levels in obese Cbl-b(-/-) mice. |
| 780 | 23349502 | These results suggest that Cbl-b deficiency could exaggerate HFD-induced insulin resistance through saturated FA-mediated macrophage activation. |
| 781 | 23349502 | Therefore, inhibition of TLR4 signaling is an attractive therapeutic strategy for treatment of obesity-related insulin resistance. |
| 782 | 23382179 | Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a key regulator of the innate immune system, particularly in the skin where, in response to molecular triggers such as pathogen-associated or damage-associated molecular patterns, the NLRP1 inflammasome promotes caspase-1-dependent processing of bioactive interleukin-1β (IL-1β), resulting in IL-1β secretion and downstream inflammatory responses. |
| 783 | 23382179 | Functionally, we found that peripheral blood monocytes from healthy subjects homozygous for the predominant high-risk haplotype 2A processed significantly greater (P < 0.0001) amounts of the IL-1β precursor to mature bioactive IL-1β under basal (resting) conditions and in response to Toll-like receptor (TLR) agonists (TLR2 and TLR4) compared with monocytes from subjects homozygous for the reference haplotype 1. |
| 784 | 23390498 | SGLT1 and 2 expression and various inflammatory/fibrotic markers were assessed. |
| 785 | 23390498 | A chromatin immunoprecipitation assay was used to determine the binding of phosphorylated smad3 to the promoter region of the SGLT2 gene. |
| 786 | 23390498 | HG induced expression of Toll-like receptor-4, increased nuclear deoxyribonucleic acid binding for nuclear factor kappa B (NF-κB) and activator protein 1, induced collagen IV expression as well as interleukin-6 secretion all of which were attenuated with empagliflozin. |
| 787 | 23390498 | SGLT1 and GLUT2 expression was not significantly altered with HG or empagliflozin. |
| 788 | 23390498 | In conclusion, empagliflozin reduces HG induced inflammatory and fibrotic markers by blocking glucose transport and did not induce a compensatory increase in SGLT1/GLUT2 expression. |
| 789 | 23413427 | Toll-like receptor 4 mutation protects obese mice against endothelial dysfunction by decreasing NADPH oxidase isoforms 1 and 4. |
| 790 | 23423259 | Here we explored whether the TLR4 antagonist, CRX-526, has therapeutic potential to attenuate renal injuries and slow the progression of advanced diabetic nephropathy in wild-type and endothelial nitric oxide synthase (eNOS) knockout mice. |
| 791 | 23423259 | In the latter, the endogenous TLR4 ligand, high-mobility group box 1, was upregulated more than in wild-type animals. |
| 792 | 23423259 | Glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial injury were attenuated by CRX-526, which was associated with decreased chemokine (C-C motif) ligand (CCL)-2, osteopontin, CCL-5 overexpression, subsequent macrophage infiltration, and collagen deposition. |
| 793 | 23423259 | Thus, we provided evidence that inhibition of TLR4 with the synthetic antagonist CRX-526 conferred renoprotective effects in eNOS knockout diabetic mice with advanced diabetic nephropathy. |
| 794 | 23423259 | Here we explored whether the TLR4 antagonist, CRX-526, has therapeutic potential to attenuate renal injuries and slow the progression of advanced diabetic nephropathy in wild-type and endothelial nitric oxide synthase (eNOS) knockout mice. |
| 795 | 23423259 | In the latter, the endogenous TLR4 ligand, high-mobility group box 1, was upregulated more than in wild-type animals. |
| 796 | 23423259 | Glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial injury were attenuated by CRX-526, which was associated with decreased chemokine (C-C motif) ligand (CCL)-2, osteopontin, CCL-5 overexpression, subsequent macrophage infiltration, and collagen deposition. |
| 797 | 23423259 | Thus, we provided evidence that inhibition of TLR4 with the synthetic antagonist CRX-526 conferred renoprotective effects in eNOS knockout diabetic mice with advanced diabetic nephropathy. |
| 798 | 23423259 | Here we explored whether the TLR4 antagonist, CRX-526, has therapeutic potential to attenuate renal injuries and slow the progression of advanced diabetic nephropathy in wild-type and endothelial nitric oxide synthase (eNOS) knockout mice. |
| 799 | 23423259 | In the latter, the endogenous TLR4 ligand, high-mobility group box 1, was upregulated more than in wild-type animals. |
| 800 | 23423259 | Glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial injury were attenuated by CRX-526, which was associated with decreased chemokine (C-C motif) ligand (CCL)-2, osteopontin, CCL-5 overexpression, subsequent macrophage infiltration, and collagen deposition. |
| 801 | 23423259 | Thus, we provided evidence that inhibition of TLR4 with the synthetic antagonist CRX-526 conferred renoprotective effects in eNOS knockout diabetic mice with advanced diabetic nephropathy. |
| 802 | 23426369 | The enzyme acyl-CoA synthetase 1 (ACSL1) is induced by peroxisome proliferator-activated receptor α (PPARα) and PPARγ in insulin target tissues, such as skeletal muscle and adipose tissue, and plays an important role in β-oxidation in these tissues. |
| 803 | 23426369 | LPS, Gram-negative bacteria, IFN-γ, and TNFα all induce ACSL1 expression in macrophages, whereas PPAR agonists do not. |
| 804 | 23426369 | LPS-induced ACSL1 expression is dependent on Toll-like receptor 4 (TLR4) and its adaptor protein TRIF (Toll-like receptor adaptor molecule 1) but does not require the MyD88 (myeloid differentiation primary response gene 88) arm of TLR4 signaling; nor does it require STAT1 (signal transducer and activator of transcription 1) for maximal induction. |
| 805 | 23426369 | Thus, the regulation and biological function of ACSL1 in macrophages differ markedly from that in insulin target tissues. |
| 806 | 23436141 | Here we review some of the most promising drugs and agents that have the potential to attenuate TLR-mediated inflammation, e.g., anti-LPS strategies that aim to neutralize LPS (synthetic anti-LPS peptides and recombinant factor C) and TLR4/MyD88 antagonists, including eritoran, CyP, EM-163, epigallocatechin-3-gallate, 6-shogaol, cinnamon extract, N-acetylcysteine, melatonin, and molecular hydrogen. |
| 807 | 23454694 | Several mechanisms, such as innate immune responses via Toll-like receptor-4, accumulation of diacylglycerols (DAG)/ceramides, and activation of protein kinase C (PKC), are considered to underlie skeletal muscle insulin resistance. |
| 808 | 23454694 | Only after LPS, circulating inflammatory markers (tumor necrosis factor-α, interleukin-6, and interleukin-1 receptor antagonist), their mRNA expression in subcutaneous adipose tissue, and circulating cortisol were elevated. |
| 809 | 23465595 | This study examined the role of TLR4 in mediating palmitate effects on the expression of phosphoenolpyruvate carboxykinase (PCK1) and the catalytic subunit of glucose-6-phosphatase (G6PC), rate-determining gluconeogenic enzymes. |
| 810 | 23465595 | Palmitate induced dose-dependent increases in PCK1 and G6PC mRNA abundance, which were prevented by the TLR4 decoy peptide. |
| 811 | 23465595 | Palmitate doubled PCK1 promoter activity, and TLR4 knockdown ablated this response. |
| 812 | 23465595 | Lipopolysaccharide and monophosphoryl lipid A also up-regulated G6PC and PCK1 transcript abundance in a TLR4-dependent manner. |
| 813 | 23465595 | Addition of oleate attenuated palmitate-induced increases in G6PC and PCK1 mRNA abundance. |
| 814 | 23465595 | Palmitate increased nuclear factor κ-light-chain-enhancer of activated B cells reporter gene activity, which was unaffected by TLR4 blockade, but increased mRNA abundance of hepatocyte-specific cyclic AMP response element binding protein, a transcriptional regulator of PCK1, in a TLR4-dependent manner. |
| 815 | 23465595 | Finally, TLR4 activation by palmitate increased subsequent cellular uptake of palmitate, and inhibiting ceramide synthesis ablated palmitate effects on PCK1 mRNA abundance and promoter activity. |
| 816 | 23465595 | This study examined the role of TLR4 in mediating palmitate effects on the expression of phosphoenolpyruvate carboxykinase (PCK1) and the catalytic subunit of glucose-6-phosphatase (G6PC), rate-determining gluconeogenic enzymes. |
| 817 | 23465595 | Palmitate induced dose-dependent increases in PCK1 and G6PC mRNA abundance, which were prevented by the TLR4 decoy peptide. |
| 818 | 23465595 | Palmitate doubled PCK1 promoter activity, and TLR4 knockdown ablated this response. |
| 819 | 23465595 | Lipopolysaccharide and monophosphoryl lipid A also up-regulated G6PC and PCK1 transcript abundance in a TLR4-dependent manner. |
| 820 | 23465595 | Addition of oleate attenuated palmitate-induced increases in G6PC and PCK1 mRNA abundance. |
| 821 | 23465595 | Palmitate increased nuclear factor κ-light-chain-enhancer of activated B cells reporter gene activity, which was unaffected by TLR4 blockade, but increased mRNA abundance of hepatocyte-specific cyclic AMP response element binding protein, a transcriptional regulator of PCK1, in a TLR4-dependent manner. |
| 822 | 23465595 | Finally, TLR4 activation by palmitate increased subsequent cellular uptake of palmitate, and inhibiting ceramide synthesis ablated palmitate effects on PCK1 mRNA abundance and promoter activity. |
| 823 | 23465595 | This study examined the role of TLR4 in mediating palmitate effects on the expression of phosphoenolpyruvate carboxykinase (PCK1) and the catalytic subunit of glucose-6-phosphatase (G6PC), rate-determining gluconeogenic enzymes. |
| 824 | 23465595 | Palmitate induced dose-dependent increases in PCK1 and G6PC mRNA abundance, which were prevented by the TLR4 decoy peptide. |
| 825 | 23465595 | Palmitate doubled PCK1 promoter activity, and TLR4 knockdown ablated this response. |
| 826 | 23465595 | Lipopolysaccharide and monophosphoryl lipid A also up-regulated G6PC and PCK1 transcript abundance in a TLR4-dependent manner. |
| 827 | 23465595 | Addition of oleate attenuated palmitate-induced increases in G6PC and PCK1 mRNA abundance. |
| 828 | 23465595 | Palmitate increased nuclear factor κ-light-chain-enhancer of activated B cells reporter gene activity, which was unaffected by TLR4 blockade, but increased mRNA abundance of hepatocyte-specific cyclic AMP response element binding protein, a transcriptional regulator of PCK1, in a TLR4-dependent manner. |
| 829 | 23465595 | Finally, TLR4 activation by palmitate increased subsequent cellular uptake of palmitate, and inhibiting ceramide synthesis ablated palmitate effects on PCK1 mRNA abundance and promoter activity. |
| 830 | 23465595 | This study examined the role of TLR4 in mediating palmitate effects on the expression of phosphoenolpyruvate carboxykinase (PCK1) and the catalytic subunit of glucose-6-phosphatase (G6PC), rate-determining gluconeogenic enzymes. |
| 831 | 23465595 | Palmitate induced dose-dependent increases in PCK1 and G6PC mRNA abundance, which were prevented by the TLR4 decoy peptide. |
| 832 | 23465595 | Palmitate doubled PCK1 promoter activity, and TLR4 knockdown ablated this response. |
| 833 | 23465595 | Lipopolysaccharide and monophosphoryl lipid A also up-regulated G6PC and PCK1 transcript abundance in a TLR4-dependent manner. |
| 834 | 23465595 | Addition of oleate attenuated palmitate-induced increases in G6PC and PCK1 mRNA abundance. |
| 835 | 23465595 | Palmitate increased nuclear factor κ-light-chain-enhancer of activated B cells reporter gene activity, which was unaffected by TLR4 blockade, but increased mRNA abundance of hepatocyte-specific cyclic AMP response element binding protein, a transcriptional regulator of PCK1, in a TLR4-dependent manner. |
| 836 | 23465595 | Finally, TLR4 activation by palmitate increased subsequent cellular uptake of palmitate, and inhibiting ceramide synthesis ablated palmitate effects on PCK1 mRNA abundance and promoter activity. |
| 837 | 23465595 | This study examined the role of TLR4 in mediating palmitate effects on the expression of phosphoenolpyruvate carboxykinase (PCK1) and the catalytic subunit of glucose-6-phosphatase (G6PC), rate-determining gluconeogenic enzymes. |
| 838 | 23465595 | Palmitate induced dose-dependent increases in PCK1 and G6PC mRNA abundance, which were prevented by the TLR4 decoy peptide. |
| 839 | 23465595 | Palmitate doubled PCK1 promoter activity, and TLR4 knockdown ablated this response. |
| 840 | 23465595 | Lipopolysaccharide and monophosphoryl lipid A also up-regulated G6PC and PCK1 transcript abundance in a TLR4-dependent manner. |
| 841 | 23465595 | Addition of oleate attenuated palmitate-induced increases in G6PC and PCK1 mRNA abundance. |
| 842 | 23465595 | Palmitate increased nuclear factor κ-light-chain-enhancer of activated B cells reporter gene activity, which was unaffected by TLR4 blockade, but increased mRNA abundance of hepatocyte-specific cyclic AMP response element binding protein, a transcriptional regulator of PCK1, in a TLR4-dependent manner. |
| 843 | 23465595 | Finally, TLR4 activation by palmitate increased subsequent cellular uptake of palmitate, and inhibiting ceramide synthesis ablated palmitate effects on PCK1 mRNA abundance and promoter activity. |
| 844 | 23465595 | This study examined the role of TLR4 in mediating palmitate effects on the expression of phosphoenolpyruvate carboxykinase (PCK1) and the catalytic subunit of glucose-6-phosphatase (G6PC), rate-determining gluconeogenic enzymes. |
| 845 | 23465595 | Palmitate induced dose-dependent increases in PCK1 and G6PC mRNA abundance, which were prevented by the TLR4 decoy peptide. |
| 846 | 23465595 | Palmitate doubled PCK1 promoter activity, and TLR4 knockdown ablated this response. |
| 847 | 23465595 | Lipopolysaccharide and monophosphoryl lipid A also up-regulated G6PC and PCK1 transcript abundance in a TLR4-dependent manner. |
| 848 | 23465595 | Addition of oleate attenuated palmitate-induced increases in G6PC and PCK1 mRNA abundance. |
| 849 | 23465595 | Palmitate increased nuclear factor κ-light-chain-enhancer of activated B cells reporter gene activity, which was unaffected by TLR4 blockade, but increased mRNA abundance of hepatocyte-specific cyclic AMP response element binding protein, a transcriptional regulator of PCK1, in a TLR4-dependent manner. |
| 850 | 23465595 | Finally, TLR4 activation by palmitate increased subsequent cellular uptake of palmitate, and inhibiting ceramide synthesis ablated palmitate effects on PCK1 mRNA abundance and promoter activity. |
| 851 | 23554538 | Laser-scanning confocal microscopy showed that the TLR4-positive region did not coincide with the podoplanin-positive region but coincide with the PECAM-1- and VE-cadherin-positive regions in the glomeruli of the ICR-STZ and KK/Ta-HF. |
| 852 | 23555084 | Flii has the potential to modulate inflammation through its interaction with MyD88 which it an adaptor protein for TLR4. |
| 853 | 23555084 | When Flii levels were reduced in diabetic wounds of Flii-deficient mice, healing was improved and decreased levels of TLR4 were observed. |
| 854 | 23555084 | In contrast, increasing the level of Flii in diabetic mouse wounds led to increased TLR4 and NF- κ B production. |
| 855 | 23555084 | Treatment of murine diabetic wounds with neutralising antibodies to Flii led to an improvement in healing with decreased expression of TLR4. |
| 856 | 23555084 | Flii has the potential to modulate inflammation through its interaction with MyD88 which it an adaptor protein for TLR4. |
| 857 | 23555084 | When Flii levels were reduced in diabetic wounds of Flii-deficient mice, healing was improved and decreased levels of TLR4 were observed. |
| 858 | 23555084 | In contrast, increasing the level of Flii in diabetic mouse wounds led to increased TLR4 and NF- κ B production. |
| 859 | 23555084 | Treatment of murine diabetic wounds with neutralising antibodies to Flii led to an improvement in healing with decreased expression of TLR4. |
| 860 | 23555084 | Flii has the potential to modulate inflammation through its interaction with MyD88 which it an adaptor protein for TLR4. |
| 861 | 23555084 | When Flii levels were reduced in diabetic wounds of Flii-deficient mice, healing was improved and decreased levels of TLR4 were observed. |
| 862 | 23555084 | In contrast, increasing the level of Flii in diabetic mouse wounds led to increased TLR4 and NF- κ B production. |
| 863 | 23555084 | Treatment of murine diabetic wounds with neutralising antibodies to Flii led to an improvement in healing with decreased expression of TLR4. |
| 864 | 23555084 | Flii has the potential to modulate inflammation through its interaction with MyD88 which it an adaptor protein for TLR4. |
| 865 | 23555084 | When Flii levels were reduced in diabetic wounds of Flii-deficient mice, healing was improved and decreased levels of TLR4 were observed. |
| 866 | 23555084 | In contrast, increasing the level of Flii in diabetic mouse wounds led to increased TLR4 and NF- κ B production. |
| 867 | 23555084 | Treatment of murine diabetic wounds with neutralising antibodies to Flii led to an improvement in healing with decreased expression of TLR4. |
| 868 | 23568555 | Recent evidence suggests that activation of Toll-like receptor (TLR) signaling induces peripheral insulin resistance and mediates central insulin and leptin resistance. |
| 869 | 23568555 | Eight-week-old db/db mice were treated for 12 weeks with (S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (GIT27), which targets macrophages through the inhibition of TLR4- and TLR2/6-mediated signaling pathways. |
| 870 | 23576640 | TLR2 and 4 are present in proximal tubular cells and are activated by endogenous ligands upregulated in diabetic nephropathy, including high-mobility group box-1 (HMGB1) and fibronectin. |
| 871 | 23576640 | Glucose (11.2 mM) maximally increased TLR2 and 4 expression, HMGB1 release, and NF-κB activation with increased expression of cytokines. |
| 872 | 23576640 | Recombinant HMGB1 induced NF-κB activation, which was prevented by both TLR2 silencing [small interfering (si)RNA] and TLR4 inhibition. |
| 873 | 23576640 | Therefore, short-term moderate increases in glucose in vitro increase HMGB1, which mediates NF-κB activation through both TLR2 and 4. |
| 874 | 23576640 | Furthermore, in vivo, streptozotocin-induced diabetic mice exhibited an increase in tubular TLR2 and HMGB1 expression. |
| 875 | 23576640 | TLR2 and 4 are present in proximal tubular cells and are activated by endogenous ligands upregulated in diabetic nephropathy, including high-mobility group box-1 (HMGB1) and fibronectin. |
| 876 | 23576640 | Glucose (11.2 mM) maximally increased TLR2 and 4 expression, HMGB1 release, and NF-κB activation with increased expression of cytokines. |
| 877 | 23576640 | Recombinant HMGB1 induced NF-κB activation, which was prevented by both TLR2 silencing [small interfering (si)RNA] and TLR4 inhibition. |
| 878 | 23576640 | Therefore, short-term moderate increases in glucose in vitro increase HMGB1, which mediates NF-κB activation through both TLR2 and 4. |
| 879 | 23576640 | Furthermore, in vivo, streptozotocin-induced diabetic mice exhibited an increase in tubular TLR2 and HMGB1 expression. |
| 880 | 23576640 | TLR2 and 4 are present in proximal tubular cells and are activated by endogenous ligands upregulated in diabetic nephropathy, including high-mobility group box-1 (HMGB1) and fibronectin. |
| 881 | 23576640 | Glucose (11.2 mM) maximally increased TLR2 and 4 expression, HMGB1 release, and NF-κB activation with increased expression of cytokines. |
| 882 | 23576640 | Recombinant HMGB1 induced NF-κB activation, which was prevented by both TLR2 silencing [small interfering (si)RNA] and TLR4 inhibition. |
| 883 | 23576640 | Therefore, short-term moderate increases in glucose in vitro increase HMGB1, which mediates NF-κB activation through both TLR2 and 4. |
| 884 | 23576640 | Furthermore, in vivo, streptozotocin-induced diabetic mice exhibited an increase in tubular TLR2 and HMGB1 expression. |
| 885 | 23576640 | TLR2 and 4 are present in proximal tubular cells and are activated by endogenous ligands upregulated in diabetic nephropathy, including high-mobility group box-1 (HMGB1) and fibronectin. |
| 886 | 23576640 | Glucose (11.2 mM) maximally increased TLR2 and 4 expression, HMGB1 release, and NF-κB activation with increased expression of cytokines. |
| 887 | 23576640 | Recombinant HMGB1 induced NF-κB activation, which was prevented by both TLR2 silencing [small interfering (si)RNA] and TLR4 inhibition. |
| 888 | 23576640 | Therefore, short-term moderate increases in glucose in vitro increase HMGB1, which mediates NF-κB activation through both TLR2 and 4. |
| 889 | 23576640 | Furthermore, in vivo, streptozotocin-induced diabetic mice exhibited an increase in tubular TLR2 and HMGB1 expression. |
| 890 | 23671849 | This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK) phosphorylation. |
| 891 | 23671849 | TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. |
| 892 | 23671849 | While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals. |
| 893 | 23671849 | This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK) phosphorylation. |
| 894 | 23671849 | TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. |
| 895 | 23671849 | While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals. |
| 896 | 23671849 | This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK) phosphorylation. |
| 897 | 23671849 | TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. |
| 898 | 23671849 | While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals. |
| 899 | 23704966 | Plasma LPS (r = -0.46, P = 0.005) and LBP (r = -0.49, P = 0.005) concentrations negatively correlated with muscle insulin sensitivity (M). |
| 900 | 23704966 | In human myotubes, LPS increased JNK phosphorylation and MCP-1 and IL-6 gene expression. |
| 901 | 23704966 | This inflammatory response led to reduced insulin-stimulated IRS-1, Akt and AS160 phosphorylation and impaired glucose transport. |
| 902 | 23704966 | Both pharmacologic blockade of TLR4 with TAK-242, and TLR4 gene silencing, suppressed the inflammatory response and insulin resistance caused by LPS in human muscle cells. |
| 903 | 23704966 | Taken together, these findings suggest that elevations in plasma LPS concentration found in obese and T2DM subjects could play a role in the pathogenesis of insulin resistance and that antagonists of TLR4 may improve insulin action in these individuals. |
| 904 | 23704966 | Plasma LPS (r = -0.46, P = 0.005) and LBP (r = -0.49, P = 0.005) concentrations negatively correlated with muscle insulin sensitivity (M). |
| 905 | 23704966 | In human myotubes, LPS increased JNK phosphorylation and MCP-1 and IL-6 gene expression. |
| 906 | 23704966 | This inflammatory response led to reduced insulin-stimulated IRS-1, Akt and AS160 phosphorylation and impaired glucose transport. |
| 907 | 23704966 | Both pharmacologic blockade of TLR4 with TAK-242, and TLR4 gene silencing, suppressed the inflammatory response and insulin resistance caused by LPS in human muscle cells. |
| 908 | 23704966 | Taken together, these findings suggest that elevations in plasma LPS concentration found in obese and T2DM subjects could play a role in the pathogenesis of insulin resistance and that antagonists of TLR4 may improve insulin action in these individuals. |
| 909 | 23714175 | Oral Angiotensin-(1-7) prevented obesity and hepatic inflammation by inhibition of resistin/TLR4/MAPK/NF-κB in rats fed with high-fat diet. |
| 910 | 23714175 | RT-PCR evaluated mRNA expression to ACE, ACE2, resistin, TLR4, IL-6, TNF-α and NF-κB genes. |
| 911 | 23714175 | These alterations were accompanied by a marked decreased expression of resistin, TLR4, ACE and increased ACE2 expression in liver. |
| 912 | 23714175 | Oral Angiotensin-(1-7) prevented obesity and hepatic inflammation by inhibition of resistin/TLR4/MAPK/NF-κB in rats fed with high-fat diet. |
| 913 | 23714175 | RT-PCR evaluated mRNA expression to ACE, ACE2, resistin, TLR4, IL-6, TNF-α and NF-κB genes. |
| 914 | 23714175 | These alterations were accompanied by a marked decreased expression of resistin, TLR4, ACE and increased ACE2 expression in liver. |
| 915 | 23714175 | Oral Angiotensin-(1-7) prevented obesity and hepatic inflammation by inhibition of resistin/TLR4/MAPK/NF-κB in rats fed with high-fat diet. |
| 916 | 23714175 | RT-PCR evaluated mRNA expression to ACE, ACE2, resistin, TLR4, IL-6, TNF-α and NF-κB genes. |
| 917 | 23714175 | These alterations were accompanied by a marked decreased expression of resistin, TLR4, ACE and increased ACE2 expression in liver. |
| 918 | 23735822 | As a metabolic disorder depression has been associated with obesity, diabetes, insulin sensitivity, neuropeptide Y, glucose regulation, poor glycemic control, glucagone-like peptide-1, cholezystokinin, ghrelin, leptin, the endocannabinoid system, insulin-like growth factor and gastrin-releasing peptide. |
| 919 | 23735822 | Additionally blood coagulation, fibrinolysis, D-dimers, plasminogen activator inhibitor-1 protein, platelet activation, VEGF, plasma nitric oxide and its synthase are changed in depressed patients. |
| 920 | 23735822 | As an endocrinological and stress disorder depression has been connected with the concentration of free T4, TSH, CRH, arginine vasopressin, corticotrophin, corticosteroid release and ACTH. |
| 921 | 23735822 | Depression as an inflammatory disorder is mediated by pro-inflammatory cytokines, interleukin-1, interleukin-6, TNF-alpha, soluble interleukin-2 receptors, interferon-alpha, interleukin 8, interleukin-10, hs-CRP, acute phase proteins, haptoglobin, toll like receptor 4, interleukin-1beta, mammalian target of rapamycin pathway, substance P, cyclooxygenase-2, prostaglandin-E2, lipid peroxidation levels and acid sphingomyelinase. |
| 922 | 23735822 | The neurodegenerative hypothesis of depression explains decreased hippocampal volumes in depressed patients and changes of neurotrophic support by BDNF, erythropoietin, GDNF, FGF-2, NT3, NGF and growth hormone. |
| 923 | 23735822 | Hence, GABA, AMPA, EAAT, NMDA- and metabotropic glutamate receptors (mGluR1 to mGluR8) have gained interest in depression recently. |
| 924 | 23766559 | Carrageenan-induced colonic inflammation is reduced in Bcl10 null mice and increased in IL-10-deficient mice. |
| 925 | 23766559 | Since the TLR4 signaling pathway is activated in diabetes and by carrageenan, we addressed systemic and intestinal inflammatory responses following carrageenan exposure in Bcl10 wild type, heterozygous, and null mice. |
| 926 | 23766559 | Fecal calprotectin and circulating keratinocyte chemokine (KC), nuclear RelA and RelB, phospho(Thr559)-NF-κB-inducing kinase (NIK), and phospho(Ser36)-IκBα in the colonic epithelial cells were significantly less (P < 0.001) in the carrageenan-treated Bcl10 null mice than in controls. |
| 927 | 23766559 | These findings demonstrate a Bcl10 requirement for maximum development of carrageenan-induced inflammation and lack of complete suppression by IL-10 of carrageenan-induced inflammation. |
| 928 | 23773694 | IL-6, TNF-α concentration and nuclear factor-κB (NF-κB) activation were increased in diabetic wounds compared to non-diabetic wounds and knockout of TLR4 alleviates wound healing and decreases inflammation in diabetic TLR4 KO mice. |
| 929 | 23774118 | Immunohistological examination revealed the presence of enterovirus in pancreatic islet cells and exocrine tissues and hyperexpression of pattern recognition receptors (PRRs) including melanoma differentiation-associated antigen 5 (MDA5), retinoic acid-inducible gene-I (RIG-I), Toll-like receptor (TLR)3 and TLR4, essential sensors of innate immunity, in islet cells and mononuclear cells (MNCs) infiltrating islets. |
| 930 | 23774118 | Islet β-cells simultaneously expressed CXC chemokine ligand 10 (CXCL10), IFN-γ and interleukin-18, indicating that these chemokines/ cytotoxic cytokines mutually amplify their cytoplasmic expression in the islet cells. |
| 931 | 23774118 | In addition to intrinsic pathway of cell apoptosis, the Fas and Fas ligand pathway are also involved as an extrinsic pathway of cell apoptosis. |
| 932 | 23800176 | MD-2 is involved in the stimulation of matrix metalloproteinase-1 expression by interferon-γ and high glucose in mononuclear cells - a potential role of MD-2 in Toll-like receptor 4-independent signalling. |
| 933 | 23800176 | We reported recently that treatment of diabetic apolipoprotein E-deficient mice with the Toll-like receptor 4 (TLR4) antagonist Rs-LPS, a lipopolysaccharide isolated from Rhodobacter sphaeroides, inhibited atherosclerosis. |
| 934 | 23800176 | Since it is known that Rs-LPS antagonizes TLR4 by targeting TLR4 co-receptor MD-2, this finding indicates that MD-2 is a potential target for the treatment of atherosclerosis. |
| 935 | 23800176 | In this study, we determined if MD-2 is involved in the gene expression regulated by signalling pathways independent of TLR4. |
| 936 | 23800176 | To provide more evidence for a role of MD-2 in IFN-γ-stimulated MMP-1, studies using antibodies and small interfering RNA demonstrated that MD-2 blockade or knockdown attenuated the effect of IFN-γ on MMP-1. |
| 937 | 23800176 | We found that MD-2 up-regulation by IFN-γ played an essential role in the synergistic effect of IFN-γ and LPS on MMP-1 expression. |
| 938 | 23800176 | Taken together, these findings indicate that MD-2 is involved in IFN-γ signalling and IFN-γ-augmented MMP-1 up-regulation by LPS. |
| 939 | 23800176 | MD-2 is involved in the stimulation of matrix metalloproteinase-1 expression by interferon-γ and high glucose in mononuclear cells - a potential role of MD-2 in Toll-like receptor 4-independent signalling. |
| 940 | 23800176 | We reported recently that treatment of diabetic apolipoprotein E-deficient mice with the Toll-like receptor 4 (TLR4) antagonist Rs-LPS, a lipopolysaccharide isolated from Rhodobacter sphaeroides, inhibited atherosclerosis. |
| 941 | 23800176 | Since it is known that Rs-LPS antagonizes TLR4 by targeting TLR4 co-receptor MD-2, this finding indicates that MD-2 is a potential target for the treatment of atherosclerosis. |
| 942 | 23800176 | In this study, we determined if MD-2 is involved in the gene expression regulated by signalling pathways independent of TLR4. |
| 943 | 23800176 | To provide more evidence for a role of MD-2 in IFN-γ-stimulated MMP-1, studies using antibodies and small interfering RNA demonstrated that MD-2 blockade or knockdown attenuated the effect of IFN-γ on MMP-1. |
| 944 | 23800176 | We found that MD-2 up-regulation by IFN-γ played an essential role in the synergistic effect of IFN-γ and LPS on MMP-1 expression. |
| 945 | 23800176 | Taken together, these findings indicate that MD-2 is involved in IFN-γ signalling and IFN-γ-augmented MMP-1 up-regulation by LPS. |
| 946 | 23800176 | MD-2 is involved in the stimulation of matrix metalloproteinase-1 expression by interferon-γ and high glucose in mononuclear cells - a potential role of MD-2 in Toll-like receptor 4-independent signalling. |
| 947 | 23800176 | We reported recently that treatment of diabetic apolipoprotein E-deficient mice with the Toll-like receptor 4 (TLR4) antagonist Rs-LPS, a lipopolysaccharide isolated from Rhodobacter sphaeroides, inhibited atherosclerosis. |
| 948 | 23800176 | Since it is known that Rs-LPS antagonizes TLR4 by targeting TLR4 co-receptor MD-2, this finding indicates that MD-2 is a potential target for the treatment of atherosclerosis. |
| 949 | 23800176 | In this study, we determined if MD-2 is involved in the gene expression regulated by signalling pathways independent of TLR4. |
| 950 | 23800176 | To provide more evidence for a role of MD-2 in IFN-γ-stimulated MMP-1, studies using antibodies and small interfering RNA demonstrated that MD-2 blockade or knockdown attenuated the effect of IFN-γ on MMP-1. |
| 951 | 23800176 | We found that MD-2 up-regulation by IFN-γ played an essential role in the synergistic effect of IFN-γ and LPS on MMP-1 expression. |
| 952 | 23800176 | Taken together, these findings indicate that MD-2 is involved in IFN-γ signalling and IFN-γ-augmented MMP-1 up-regulation by LPS. |
| 953 | 23800176 | MD-2 is involved in the stimulation of matrix metalloproteinase-1 expression by interferon-γ and high glucose in mononuclear cells - a potential role of MD-2 in Toll-like receptor 4-independent signalling. |
| 954 | 23800176 | We reported recently that treatment of diabetic apolipoprotein E-deficient mice with the Toll-like receptor 4 (TLR4) antagonist Rs-LPS, a lipopolysaccharide isolated from Rhodobacter sphaeroides, inhibited atherosclerosis. |
| 955 | 23800176 | Since it is known that Rs-LPS antagonizes TLR4 by targeting TLR4 co-receptor MD-2, this finding indicates that MD-2 is a potential target for the treatment of atherosclerosis. |
| 956 | 23800176 | In this study, we determined if MD-2 is involved in the gene expression regulated by signalling pathways independent of TLR4. |
| 957 | 23800176 | To provide more evidence for a role of MD-2 in IFN-γ-stimulated MMP-1, studies using antibodies and small interfering RNA demonstrated that MD-2 blockade or knockdown attenuated the effect of IFN-γ on MMP-1. |
| 958 | 23800176 | We found that MD-2 up-regulation by IFN-γ played an essential role in the synergistic effect of IFN-γ and LPS on MMP-1 expression. |
| 959 | 23800176 | Taken together, these findings indicate that MD-2 is involved in IFN-γ signalling and IFN-γ-augmented MMP-1 up-regulation by LPS. |
| 960 | 23813327 | Aortas from different groups were assessed for histopathology, toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), and nuclear factor-kappa B (NF-κB) p65 expression by hematoxylin and eosin staining, immunohistochemistry staining, reverse transcription polymerase chain reaction, and Western blot analysis. |
| 961 | 23813327 | High-dose 1,25(OH)2D3 (0.3 μg/kg/day) significantly prevented diabetes-induced aortic pathological changes and collagen deposition and decreased the expression of TLR4, MyD88, and NF-κB at both mRNA and protein levels in the aorta of STZ-induced diabetic rats (P < 0.01). |
| 962 | 23813327 | Our results indicate that vitamin D has protective effects on diabetes-induced aortic injury and attenuates the expressions of TLR4, MyD88, and NF-κB in diabetic rats. |
| 963 | 23813327 | Aortas from different groups were assessed for histopathology, toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), and nuclear factor-kappa B (NF-κB) p65 expression by hematoxylin and eosin staining, immunohistochemistry staining, reverse transcription polymerase chain reaction, and Western blot analysis. |
| 964 | 23813327 | High-dose 1,25(OH)2D3 (0.3 μg/kg/day) significantly prevented diabetes-induced aortic pathological changes and collagen deposition and decreased the expression of TLR4, MyD88, and NF-κB at both mRNA and protein levels in the aorta of STZ-induced diabetic rats (P < 0.01). |
| 965 | 23813327 | Our results indicate that vitamin D has protective effects on diabetes-induced aortic injury and attenuates the expressions of TLR4, MyD88, and NF-κB in diabetic rats. |
| 966 | 23813327 | Aortas from different groups were assessed for histopathology, toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), and nuclear factor-kappa B (NF-κB) p65 expression by hematoxylin and eosin staining, immunohistochemistry staining, reverse transcription polymerase chain reaction, and Western blot analysis. |
| 967 | 23813327 | High-dose 1,25(OH)2D3 (0.3 μg/kg/day) significantly prevented diabetes-induced aortic pathological changes and collagen deposition and decreased the expression of TLR4, MyD88, and NF-κB at both mRNA and protein levels in the aorta of STZ-induced diabetic rats (P < 0.01). |
| 968 | 23813327 | Our results indicate that vitamin D has protective effects on diabetes-induced aortic injury and attenuates the expressions of TLR4, MyD88, and NF-κB in diabetic rats. |
| 969 | 23826669 | Palmitate induces interleukin-8 expression in human aortic vascular smooth muscle cells via Toll-like receptor 4/nuclear factor-κB pathway (TLR4/NF-κB-8). |
| 970 | 23840067 | Saturated and unsaturated fat induce hepatic insulin resistance independently of TLR-4 signaling and ceramide synthesis in vivo. |
| 971 | 23840067 | Recent studies have suggested that saturated fatty acids induce hepatic insulin resistance through activation of the toll-like receptor 4 (TLR-4) receptor in the liver, which in turn transcriptionally activates hepatic ceramide synthesis leading to inhibition of insulin signaling. |
| 972 | 23840067 | In this study, we demonstrate that TLR-4 receptor signaling is not directly required for saturated or unsaturated fat-induced hepatic insulin resistance in both TLR-4 antisense oligonucleotide treated and TLR-4 knockout mice, and that ceramide accumulation is not dependent on TLR-4 signaling or a primary event in hepatic steatosis and impairment of insulin signaling. |
| 973 | 23840067 | Further, we show that both saturated and unsaturated fats lead to hepatic accumulation of diacylglycerols, activation of PKCε, and impairment of insulin-stimulated IRS-2 signaling. |
| 974 | 23840067 | These data demonstrate that saturated fat-induced insulin resistance is independent of TLR-4 activation and ceramides. |
| 975 | 23840067 | Saturated and unsaturated fat induce hepatic insulin resistance independently of TLR-4 signaling and ceramide synthesis in vivo. |
| 976 | 23840067 | Recent studies have suggested that saturated fatty acids induce hepatic insulin resistance through activation of the toll-like receptor 4 (TLR-4) receptor in the liver, which in turn transcriptionally activates hepatic ceramide synthesis leading to inhibition of insulin signaling. |
| 977 | 23840067 | In this study, we demonstrate that TLR-4 receptor signaling is not directly required for saturated or unsaturated fat-induced hepatic insulin resistance in both TLR-4 antisense oligonucleotide treated and TLR-4 knockout mice, and that ceramide accumulation is not dependent on TLR-4 signaling or a primary event in hepatic steatosis and impairment of insulin signaling. |
| 978 | 23840067 | Further, we show that both saturated and unsaturated fats lead to hepatic accumulation of diacylglycerols, activation of PKCε, and impairment of insulin-stimulated IRS-2 signaling. |
| 979 | 23840067 | These data demonstrate that saturated fat-induced insulin resistance is independent of TLR-4 activation and ceramides. |
| 980 | 23840067 | Saturated and unsaturated fat induce hepatic insulin resistance independently of TLR-4 signaling and ceramide synthesis in vivo. |
| 981 | 23840067 | Recent studies have suggested that saturated fatty acids induce hepatic insulin resistance through activation of the toll-like receptor 4 (TLR-4) receptor in the liver, which in turn transcriptionally activates hepatic ceramide synthesis leading to inhibition of insulin signaling. |
| 982 | 23840067 | In this study, we demonstrate that TLR-4 receptor signaling is not directly required for saturated or unsaturated fat-induced hepatic insulin resistance in both TLR-4 antisense oligonucleotide treated and TLR-4 knockout mice, and that ceramide accumulation is not dependent on TLR-4 signaling or a primary event in hepatic steatosis and impairment of insulin signaling. |
| 983 | 23840067 | Further, we show that both saturated and unsaturated fats lead to hepatic accumulation of diacylglycerols, activation of PKCε, and impairment of insulin-stimulated IRS-2 signaling. |
| 984 | 23840067 | These data demonstrate that saturated fat-induced insulin resistance is independent of TLR-4 activation and ceramides. |
| 985 | 23840067 | Saturated and unsaturated fat induce hepatic insulin resistance independently of TLR-4 signaling and ceramide synthesis in vivo. |
| 986 | 23840067 | Recent studies have suggested that saturated fatty acids induce hepatic insulin resistance through activation of the toll-like receptor 4 (TLR-4) receptor in the liver, which in turn transcriptionally activates hepatic ceramide synthesis leading to inhibition of insulin signaling. |
| 987 | 23840067 | In this study, we demonstrate that TLR-4 receptor signaling is not directly required for saturated or unsaturated fat-induced hepatic insulin resistance in both TLR-4 antisense oligonucleotide treated and TLR-4 knockout mice, and that ceramide accumulation is not dependent on TLR-4 signaling or a primary event in hepatic steatosis and impairment of insulin signaling. |
| 988 | 23840067 | Further, we show that both saturated and unsaturated fats lead to hepatic accumulation of diacylglycerols, activation of PKCε, and impairment of insulin-stimulated IRS-2 signaling. |
| 989 | 23840067 | These data demonstrate that saturated fat-induced insulin resistance is independent of TLR-4 activation and ceramides. |
| 990 | 23909843 | While SFAs have been shown to induce inflammation, PUFAs have anti-inflammatory effects by downregulating NF-kappaB, IL-1β, TNF-α and IL-6 despite upregulating of IL-10. |
| 991 | 23909843 | It is suggested that FFA may activate Toll Like Receptor-4 (TLR4) and G protein-coupled receptors (GPCR) activating signaling pathways that promote production and release of inflammatory cytokines (IL-6 and TFN-α). |
| 992 | 23909843 | Fatty acid action on TLR4, peroxisome proliferator-activated receptors (PPARs) and GPCRs are potential therapeutic targets for controlling FFA-induced inflammation. |
| 993 | 23909843 | While SFAs have been shown to induce inflammation, PUFAs have anti-inflammatory effects by downregulating NF-kappaB, IL-1β, TNF-α and IL-6 despite upregulating of IL-10. |
| 994 | 23909843 | It is suggested that FFA may activate Toll Like Receptor-4 (TLR4) and G protein-coupled receptors (GPCR) activating signaling pathways that promote production and release of inflammatory cytokines (IL-6 and TFN-α). |
| 995 | 23909843 | Fatty acid action on TLR4, peroxisome proliferator-activated receptors (PPARs) and GPCRs are potential therapeutic targets for controlling FFA-induced inflammation. |
| 996 | 23921144 | Besides IL-6, PA amplified the stimulatory effect of LPS on a large amount of Toll-like receptor (TLR)4-mediated expression of proinflammatory signaling molecules such as IL-1 receptor-associated kinase-like 2 and proinflammatory molecules, including monocyte chemotactic protein-1 and colony-stimulating factor. |
| 997 | 23921144 | We also observed that PA augmented TLR4 but not TLR2 signal, and the augmentation was mediated by nuclear factor-κB (NF-κB) pathways. |
| 998 | 23921144 | To further elucidate the regulatory mechanism whereby PA amplifies LPS signal, our studies showed that PA and LPS synergistically increased hydrolysis of sphingomyelin by stimulating acid sphingomyelinase (ASMase) activity, which contributed to a marked increase in ceramide production and IL-6 upregulation. |
| 999 | 23928875 | We first demonstrated high-glucose-induced HMGB1 translocation from nucleus to cytosol, and this translocation was induced through a NADPH oxidase and PKC-dependent pathway. |
| 1000 | 23928875 | We next found high glucose also increased TLR2, TLR4, and RAGE expression. |
| 1001 | 23928875 | Then, we revealed downregulating HMGB1 expression abolished high-glucose-induced calcification accompanied by NFκB inactivation and low expression of bone morphogenetic protein-2 (BMP-2). |
| 1002 | 23928875 | Our findings thus suggest HMGB1 plays an important role in mediating the calcification process induced by high glucose through NFκB activation and BMP-2 expression in VSMC of saphenous vein. |
| 1003 | 23985305 | The results from biological characteristics, glucose tolerance test, insulin tolerance test, and insulin release test showed that the function of pancreatic islet was impaired in HF-fed TLR4 WT mice, but was protected in HF-fed TLR4 deficient (TLR4(-/-)) mice. |
| 1004 | 23985305 | By electron microscope detection, we observed that beta cell insulin secretory vesicles increased in HF-fed TLR4 WT mice. |
| 1005 | 23985305 | Then, glucose-stimulated insulin secretion assay by using primary pancreatic islet showed that the secretion function of pancreatic islet in HF-fed TLR4(-/-) mice was better than that in HF-fed TLR4 WT mice. |
| 1006 | 23985305 | Furthermore, in HF-fed TLR4(-/-) mice, the mRNA levels of IL-6, TNF-α, and MCP-1 genes in pancreatic islet were significantly lower than those in HF-fed TLR4 WT mice. |
| 1007 | 23985305 | The results from biological characteristics, glucose tolerance test, insulin tolerance test, and insulin release test showed that the function of pancreatic islet was impaired in HF-fed TLR4 WT mice, but was protected in HF-fed TLR4 deficient (TLR4(-/-)) mice. |
| 1008 | 23985305 | By electron microscope detection, we observed that beta cell insulin secretory vesicles increased in HF-fed TLR4 WT mice. |
| 1009 | 23985305 | Then, glucose-stimulated insulin secretion assay by using primary pancreatic islet showed that the secretion function of pancreatic islet in HF-fed TLR4(-/-) mice was better than that in HF-fed TLR4 WT mice. |
| 1010 | 23985305 | Furthermore, in HF-fed TLR4(-/-) mice, the mRNA levels of IL-6, TNF-α, and MCP-1 genes in pancreatic islet were significantly lower than those in HF-fed TLR4 WT mice. |
| 1011 | 23985305 | The results from biological characteristics, glucose tolerance test, insulin tolerance test, and insulin release test showed that the function of pancreatic islet was impaired in HF-fed TLR4 WT mice, but was protected in HF-fed TLR4 deficient (TLR4(-/-)) mice. |
| 1012 | 23985305 | By electron microscope detection, we observed that beta cell insulin secretory vesicles increased in HF-fed TLR4 WT mice. |
| 1013 | 23985305 | Then, glucose-stimulated insulin secretion assay by using primary pancreatic islet showed that the secretion function of pancreatic islet in HF-fed TLR4(-/-) mice was better than that in HF-fed TLR4 WT mice. |
| 1014 | 23985305 | Furthermore, in HF-fed TLR4(-/-) mice, the mRNA levels of IL-6, TNF-α, and MCP-1 genes in pancreatic islet were significantly lower than those in HF-fed TLR4 WT mice. |
| 1015 | 23985305 | The results from biological characteristics, glucose tolerance test, insulin tolerance test, and insulin release test showed that the function of pancreatic islet was impaired in HF-fed TLR4 WT mice, but was protected in HF-fed TLR4 deficient (TLR4(-/-)) mice. |
| 1016 | 23985305 | By electron microscope detection, we observed that beta cell insulin secretory vesicles increased in HF-fed TLR4 WT mice. |
| 1017 | 23985305 | Then, glucose-stimulated insulin secretion assay by using primary pancreatic islet showed that the secretion function of pancreatic islet in HF-fed TLR4(-/-) mice was better than that in HF-fed TLR4 WT mice. |
| 1018 | 23985305 | Furthermore, in HF-fed TLR4(-/-) mice, the mRNA levels of IL-6, TNF-α, and MCP-1 genes in pancreatic islet were significantly lower than those in HF-fed TLR4 WT mice. |
| 1019 | 23990363 | Activating transcription factor 4 links metabolic stress to interleukin-6 expression in macrophages. |
| 1020 | 23990363 | Haploinsufficiency and short hairpin RNA-based knockdown of ATF4 in macrophages markedly inhibited SFA- and metabolic stress-induced Il6 expression. |
| 1021 | 23990363 | Conversely, pharmacological activation of the ATF4 pathway and overexpression of ATF4 resulted in enhanced Il6 expression. |
| 1022 | 23990363 | Moreover, ATF4 acts in synergy with the Toll-like receptor-4 signaling pathway, which is known to be activated by SFAs. |
| 1023 | 23990363 | At a molecular level, we found that ATF4 exerts its proinflammatory effects through at least two different mechanisms: ATF4 is involved in SFA-induced nuclear factor-κB activation; and ATF4 directly activates the Il6 promoter. |
| 1024 | 23990363 | These findings provide evidence suggesting that ATF4 links metabolic stress and Il6 expression in macrophages. |