Ignet

Gene Information

Gene symbol: NFKBIA

Gene name: nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha

HGNC ID: 7797

Synonyms: IKBA, MAD-3, IkappaBalpha

Related Genes

#	Gene Symbol	Number of hits
1	AKT1	1 hits
2	ATIC	1 hits
3	CARD14	1 hits
4	CASP1	1 hits
5	CAT	1 hits
6	CCL2	1 hits
7	CD40	1 hits
8	CHUK	1 hits
9	FADD	1 hits
10	FAS	1 hits
11	FOS	1 hits
12	GORASP1	1 hits
13	HLA-DRB1	1 hits
14	IFNG	1 hits
15	IKBKB	1 hits
16	IL12A	1 hits
17	IL1B	1 hits
18	IL28RA	1 hits
19	IL6	1 hits
20	ING1	1 hits
21	INS	1 hits
22	IRS1	1 hits
23	JUN	1 hits
24	LNPEP	1 hits
25	MAPK1	1 hits
26	MAPK14	1 hits
27	MAPK8	1 hits
28	NEFL	1 hits
29	NFE2L2	1 hits
30	NFKB1	1 hits
31	NOS2A	1 hits
32	PTGS2	1 hits
33	REL	1 hits
34	RELA	1 hits
35	SOD1	1 hits
36	TNF	1 hits
37	TNFAIP3	1 hits
38	TNFSF10	1 hits
39	TRAF3IP2	1 hits
40	TRPV2	1 hits
41	VDR	1 hits
42	VWS	1 hits

Related Sentences

#	PMID	Sentence
1	10523611	Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease resulting from apoptotic destruction of beta cells in the islets of Langerhans.
2	10523611	Overexpression of A20 by means of adenovirus-mediated gene transfer protects islets from IL-1beta and interferon gamma-induced apoptosis.
3	10523611	The inhibitory effect of A20 on cytokine-stimulated NO production is due to transcriptional blockade of inducible NO synthase (iNOS) induction; A20 inhibits the activation of the transcription factor nuclear factor kappaB at a level upstream of IkappaBalpha degradation.
4	10523611	We propose that A20 may have therapeutic potential as a gene therapy candidate to achieve successful islet transplantation and the cure of IDDM.
5	10837498	Here, we demonstrate that chronic high glucose (CHG) causes a dramatic increase in the release of the inflammatory cytokine tumor necrosis factor alpha (TNFalpha), at least in part through enhanced TNFalpha mRNA transcription, mediated by ROS via activation of transcription factors nuclear factor kappaB (NF-kappaB) and activating protein-1 (AP-1).
6	10837498	The following observations supported that both NF-kappaB and AP-1 mediated enhanced TNFalpha transcription by CHG: 1) A 295-base pair fragment of the proximal TNFalpha promoter containing NF-kappaB and AP-1 sites reproduced the effects of CHG on TNFalpha transcription in a luciferase reporter assay, 2) mutational analyses of both NF-kappaB and the AP-1 sites abrogated 90% of the luciferase activity, 3) gel-shift analysis using the binding sites showed activation of NF-kappaB and AP-1 in CHG nuclear extracts, and 4) Western blot analyses demonstrated elevated nuclear levels of p65 and p50 and decreased cytosolic levels of IkappaBalpha in CHG-treated monocytes.
7	10837498	That ROS acted as a key intermediate in the CHG pathway was supported by the following evidence: 1) increased superoxide levels similar to those observed with PMA or TNFalpha, 2) increased phosphorylation of stress-responsive mitogen-activated protein kinases p38 and JNK-1, 3) counteraction of the effects of CHG on TNFalpha production, the 295TNFluc reporter activity, activation of NF-kappaB, and repression of IkappaBalpha by antioxidants and p38 mitogen-activated protein kinase inhibitors.
8	10837498	Here, we demonstrate that chronic high glucose (CHG) causes a dramatic increase in the release of the inflammatory cytokine tumor necrosis factor alpha (TNFalpha), at least in part through enhanced TNFalpha mRNA transcription, mediated by ROS via activation of transcription factors nuclear factor kappaB (NF-kappaB) and activating protein-1 (AP-1).
9	10837498	The following observations supported that both NF-kappaB and AP-1 mediated enhanced TNFalpha transcription by CHG: 1) A 295-base pair fragment of the proximal TNFalpha promoter containing NF-kappaB and AP-1 sites reproduced the effects of CHG on TNFalpha transcription in a luciferase reporter assay, 2) mutational analyses of both NF-kappaB and the AP-1 sites abrogated 90% of the luciferase activity, 3) gel-shift analysis using the binding sites showed activation of NF-kappaB and AP-1 in CHG nuclear extracts, and 4) Western blot analyses demonstrated elevated nuclear levels of p65 and p50 and decreased cytosolic levels of IkappaBalpha in CHG-treated monocytes.
10	10837498	That ROS acted as a key intermediate in the CHG pathway was supported by the following evidence: 1) increased superoxide levels similar to those observed with PMA or TNFalpha, 2) increased phosphorylation of stress-responsive mitogen-activated protein kinases p38 and JNK-1, 3) counteraction of the effects of CHG on TNFalpha production, the 295TNFluc reporter activity, activation of NF-kappaB, and repression of IkappaBalpha by antioxidants and p38 mitogen-activated protein kinase inhibitors.
11	10967112	Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that inhibits beta cell function and promotes Fas-triggered apoptosis.
12	10967112	IL-1beta promotes beta cell impairment, in part, by activating NF-kappaB transcription factor-dependent signaling pathways.
13	10967112	We have examined whether beta cells could be protected from the effects of IL-1beta by overexpressing an inhibitor of NF-kappaB activity, IkappaB, by adenoviral gene transfer to intact human islets in culture.
14	10967112	Infection of islets with an adenoviral vector encoding a non-phosphorylatable, non-degradable variant of IkappaBalpha resulted in normal insulin responses to glucose in the presence of IL-1beta.
15	10967112	Furthermore, nitric oxide production was prevented and, more importantly, Fas-triggered apoptosis was inhibited following IkappaBalpha gene transfer.
16	10967112	Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that inhibits beta cell function and promotes Fas-triggered apoptosis.
17	10967112	IL-1beta promotes beta cell impairment, in part, by activating NF-kappaB transcription factor-dependent signaling pathways.
18	10967112	We have examined whether beta cells could be protected from the effects of IL-1beta by overexpressing an inhibitor of NF-kappaB activity, IkappaB, by adenoviral gene transfer to intact human islets in culture.
19	10967112	Infection of islets with an adenoviral vector encoding a non-phosphorylatable, non-degradable variant of IkappaBalpha resulted in normal insulin responses to glucose in the presence of IL-1beta.
20	10967112	Furthermore, nitric oxide production was prevented and, more importantly, Fas-triggered apoptosis was inhibited following IkappaBalpha gene transfer.
21	11238525	We measured intranuclear NFkappaB, total cellular NFkappaB, inhibitor kappaB (IkappaB)alpha, reactive oxygen species (ROS) generation, and p47(phox) subunit (a key component protein of nicotinamide adenine dinucleotide phosphate oxidase) in MNC.
22	11238525	Plasma tumor necrosis factor (TNF)-alpha, soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor type 1 (PAI-1), C-reactive protein (CRP), and interleukin (IL)-10 (antiinflammatory cytokine) concentrations were also measured as mediators of inflammatory activity that are regulated by the proinflammatory transcription factor NFkappaB.
23	11238525	MNC were separated; and the levels of intranuclear NFkappaB, total cellular NFkappaB, IkappaBalpha, and p47 (phox) subunit and ROS generation were determined.
24	11238525	Plasma was used to measure insulin glucose, TNFalpha, sICAM, MCP-1, PAI-1, CRP, and IL-10.
25	11238525	There was a fall in intranuclear NFkappaB, total cellular NFkappaB, and p47 (phox) subunit, with an increase in cellular IkappaBalpha at week 2, which persisted until week 4.
26	11238525	Plasma TNF-alpha, sICAM-1, MCP-1, and PAI-1 concentrations fell significantly at week 4.
27	11238525	Plasma IL-10 concentration increased significantly, whereas plasma CRP concentrations decreased.
28	11238525	We measured intranuclear NFkappaB, total cellular NFkappaB, inhibitor kappaB (IkappaB)alpha, reactive oxygen species (ROS) generation, and p47(phox) subunit (a key component protein of nicotinamide adenine dinucleotide phosphate oxidase) in MNC.
29	11238525	Plasma tumor necrosis factor (TNF)-alpha, soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor type 1 (PAI-1), C-reactive protein (CRP), and interleukin (IL)-10 (antiinflammatory cytokine) concentrations were also measured as mediators of inflammatory activity that are regulated by the proinflammatory transcription factor NFkappaB.
30	11238525	MNC were separated; and the levels of intranuclear NFkappaB, total cellular NFkappaB, IkappaBalpha, and p47 (phox) subunit and ROS generation were determined.
31	11238525	Plasma was used to measure insulin glucose, TNFalpha, sICAM, MCP-1, PAI-1, CRP, and IL-10.
32	11238525	There was a fall in intranuclear NFkappaB, total cellular NFkappaB, and p47 (phox) subunit, with an increase in cellular IkappaBalpha at week 2, which persisted until week 4.
33	11238525	Plasma TNF-alpha, sICAM-1, MCP-1, and PAI-1 concentrations fell significantly at week 4.
34	11238525	Plasma IL-10 concentration increased significantly, whereas plasma CRP concentrations decreased.
35	11466366	Insulin-dependent diabetes mellitus (IDDM) is characterized by the T cell-mediated destruction of insulin-producing beta cells.
36	11466366	Here we demonstrate that DCs derived from nonobese diabetic (NOD) mice, a model for IDDM, are more sensitive to various forms of stimulation compared with those from C57BL/6 and BALB/c mice, resulting in increased IL-12 secretion.
37	11466366	This property is a consequence of hyperactivation of NF-kappaB, a transcription factor known to regulate IL-12 gene expression.
38	11466366	Transfection of NOD DCs with a modified form of IkappaBalpha significantly reduced IL-12 secretion, suggesting that hyperactivation of NF-kappaB was in part responsible for increased IL-12 production.
39	11723063	In contrast to the short and transient activation of NF-kappaB in vitro, we observed a long-lasting sustained activation of NF-kappaB in the absence of decreased IkappaBalpha in mononuclear cells from patients with type 1 diabetes.
40	11723063	As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-beta peptide (Abeta) to the transmembrane receptor for AGE (RAGE) results in protein synthesis-dependent sustained activation of NF-kappaB both in vitro and in vivo.
41	11723063	Infusion of AGE-albumin into mice bearing a beta-globin reporter transgene under control of NF-kappaB also resulted in prolonged expression of the reporter transgene.
42	11723063	In vitro studies showed that RAGE-expressing cells induced sustained translocation of NF-kappaB (p50/p65) from the cytoplasm into the nucleus for >1 week.
43	11723063	Sustained NF-kappaB activation by ligands of RAGE was mediated by initial degradation of IkappaB proteins followed by new synthesis of NF-kappaBp65 mRNA and protein in the presence of newly synthesized IkappaBalpha and IkappaBbeta.
44	11723063	In contrast to the short and transient activation of NF-kappaB in vitro, we observed a long-lasting sustained activation of NF-kappaB in the absence of decreased IkappaBalpha in mononuclear cells from patients with type 1 diabetes.
45	11723063	As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-beta peptide (Abeta) to the transmembrane receptor for AGE (RAGE) results in protein synthesis-dependent sustained activation of NF-kappaB both in vitro and in vivo.
46	11723063	Infusion of AGE-albumin into mice bearing a beta-globin reporter transgene under control of NF-kappaB also resulted in prolonged expression of the reporter transgene.
47	11723063	In vitro studies showed that RAGE-expressing cells induced sustained translocation of NF-kappaB (p50/p65) from the cytoplasm into the nucleus for >1 week.
48	11723063	Sustained NF-kappaB activation by ligands of RAGE was mediated by initial degradation of IkappaB proteins followed by new synthesis of NF-kappaBp65 mRNA and protein in the presence of newly synthesized IkappaBalpha and IkappaBbeta.
49	11751962	We have recently demonstrated that dendritic cells (DC) prepared from nonobese diabetic (NOD) mice, a spontaneous model for insulin-dependent diabetes mellitus, exhibit elevated levels of NF-kappaB activation upon stimulation.
50	11751962	The T cell stimulatory capacity of NOD DC was suppressed by gene transfer of a modified form of IkappaBalpha, indicating a direct role for NF-kappaB in this process.
51	11751962	Furthermore, neutralization of IL-12(p70) to block autocrine-mediated activation of DC also significantly reduced the capacity of NOD DC to stimulate T cells.
52	11751962	Finally, DC from nonobese diabetes-resistant mice, a strain genotypically similar to NOD yet disease resistant, resembled BALB/c and not NOD DC in terms of the level of NF-kappaB activation, secretion of IL-12(p70) and TNF-alpha, and the capacity to stimulate T cells.
53	11751962	Therefore, elevated NF-kappaB activation and enhanced APC function are specific for the NOD genotype and correlate with the progression of insulin-dependent diabetes mellitus.
54	11796489	We show here that although insulin increased kappaB-dependent reporter gene expression and augmented nuclear translocation of the p65/RelA subunit of NFkappaB and its DNA binding, it was able to induce a time-dependent accumulation of phosphorylated and ubiquitinated IkappaBalpha without its proteolytic degradation.
55	11796489	Immunofluorescence studies revealed the presence of a large pool of phosphorylated IkappaBalpha in the nucleus of unstimulated and insulin-treated cells.
56	11796489	IkappaB kinase alpha and beta, central players in the phosphorylation of IkappaBalpha, were rapidly induced following exposure to TNFalpha but not insulin.
57	11796489	Furthermore, insulin-stimulated IkappaBalpha phosphorylation did not depend on activation of the Ras/ERK cascade.
58	11796489	Expression of a dominant-negative mutant of Akt1 or class I PI3K inhibited the insulin stimulation of PI3K/Akt1 signaling without affecting phosphorylation of IkappaBalpha.
59	11796489	Interestingly, the PI3K inhibitors wortmannin and LY294002 blocked insulin-stimulated class I PI3K-dependent events at much lower doses than that required to inhibit phosphorylation of IkappaBalpha.
60	11796489	These data demonstrate that insulin regulates IkappaBalpha function through a distinct low-affinity wortmannin-sensitive pathway.
61	11796489	We show here that although insulin increased kappaB-dependent reporter gene expression and augmented nuclear translocation of the p65/RelA subunit of NFkappaB and its DNA binding, it was able to induce a time-dependent accumulation of phosphorylated and ubiquitinated IkappaBalpha without its proteolytic degradation.
62	11796489	Immunofluorescence studies revealed the presence of a large pool of phosphorylated IkappaBalpha in the nucleus of unstimulated and insulin-treated cells.
63	11796489	IkappaB kinase alpha and beta, central players in the phosphorylation of IkappaBalpha, were rapidly induced following exposure to TNFalpha but not insulin.
64	11796489	Furthermore, insulin-stimulated IkappaBalpha phosphorylation did not depend on activation of the Ras/ERK cascade.
65	11796489	Expression of a dominant-negative mutant of Akt1 or class I PI3K inhibited the insulin stimulation of PI3K/Akt1 signaling without affecting phosphorylation of IkappaBalpha.
66	11796489	Interestingly, the PI3K inhibitors wortmannin and LY294002 blocked insulin-stimulated class I PI3K-dependent events at much lower doses than that required to inhibit phosphorylation of IkappaBalpha.
67	11796489	These data demonstrate that insulin regulates IkappaBalpha function through a distinct low-affinity wortmannin-sensitive pathway.
68	11796489	We show here that although insulin increased kappaB-dependent reporter gene expression and augmented nuclear translocation of the p65/RelA subunit of NFkappaB and its DNA binding, it was able to induce a time-dependent accumulation of phosphorylated and ubiquitinated IkappaBalpha without its proteolytic degradation.
69	11796489	Immunofluorescence studies revealed the presence of a large pool of phosphorylated IkappaBalpha in the nucleus of unstimulated and insulin-treated cells.
70	11796489	IkappaB kinase alpha and beta, central players in the phosphorylation of IkappaBalpha, were rapidly induced following exposure to TNFalpha but not insulin.
71	11796489	Furthermore, insulin-stimulated IkappaBalpha phosphorylation did not depend on activation of the Ras/ERK cascade.
72	11796489	Expression of a dominant-negative mutant of Akt1 or class I PI3K inhibited the insulin stimulation of PI3K/Akt1 signaling without affecting phosphorylation of IkappaBalpha.
73	11796489	Interestingly, the PI3K inhibitors wortmannin and LY294002 blocked insulin-stimulated class I PI3K-dependent events at much lower doses than that required to inhibit phosphorylation of IkappaBalpha.
74	11796489	These data demonstrate that insulin regulates IkappaBalpha function through a distinct low-affinity wortmannin-sensitive pathway.
75	11796489	We show here that although insulin increased kappaB-dependent reporter gene expression and augmented nuclear translocation of the p65/RelA subunit of NFkappaB and its DNA binding, it was able to induce a time-dependent accumulation of phosphorylated and ubiquitinated IkappaBalpha without its proteolytic degradation.
76	11796489	Immunofluorescence studies revealed the presence of a large pool of phosphorylated IkappaBalpha in the nucleus of unstimulated and insulin-treated cells.
77	11796489	IkappaB kinase alpha and beta, central players in the phosphorylation of IkappaBalpha, were rapidly induced following exposure to TNFalpha but not insulin.
78	11796489	Furthermore, insulin-stimulated IkappaBalpha phosphorylation did not depend on activation of the Ras/ERK cascade.
79	11796489	Expression of a dominant-negative mutant of Akt1 or class I PI3K inhibited the insulin stimulation of PI3K/Akt1 signaling without affecting phosphorylation of IkappaBalpha.
80	11796489	Interestingly, the PI3K inhibitors wortmannin and LY294002 blocked insulin-stimulated class I PI3K-dependent events at much lower doses than that required to inhibit phosphorylation of IkappaBalpha.
81	11796489	These data demonstrate that insulin regulates IkappaBalpha function through a distinct low-affinity wortmannin-sensitive pathway.
82	11796489	We show here that although insulin increased kappaB-dependent reporter gene expression and augmented nuclear translocation of the p65/RelA subunit of NFkappaB and its DNA binding, it was able to induce a time-dependent accumulation of phosphorylated and ubiquitinated IkappaBalpha without its proteolytic degradation.
83	11796489	Immunofluorescence studies revealed the presence of a large pool of phosphorylated IkappaBalpha in the nucleus of unstimulated and insulin-treated cells.
84	11796489	IkappaB kinase alpha and beta, central players in the phosphorylation of IkappaBalpha, were rapidly induced following exposure to TNFalpha but not insulin.
85	11796489	Furthermore, insulin-stimulated IkappaBalpha phosphorylation did not depend on activation of the Ras/ERK cascade.
86	11796489	Expression of a dominant-negative mutant of Akt1 or class I PI3K inhibited the insulin stimulation of PI3K/Akt1 signaling without affecting phosphorylation of IkappaBalpha.
87	11796489	Interestingly, the PI3K inhibitors wortmannin and LY294002 blocked insulin-stimulated class I PI3K-dependent events at much lower doses than that required to inhibit phosphorylation of IkappaBalpha.
88	11796489	These data demonstrate that insulin regulates IkappaBalpha function through a distinct low-affinity wortmannin-sensitive pathway.
89	11978627	Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory.
90	11978627	Tumor necrosis factor-alpha (TNF-alpha) is a contributing cause of the insulin resistance seen in obesity and obesity-linked type 2 diabetes, but the mechanism(s) by which TNF-alpha induces insulin resistance is not understood.
91	11978627	TNF-alpha-induced genes include transcription factors implicated in preadipocyte gene expression or NF-kappaB activation, cytokines and cytokine-induced proteins, growth factors, enzymes, and signaling molecules.
92	11978627	Importantly, a number of adipocyte-abundant genes, including GLUT4, hormone sensitive lipase, long-chain fatty acyl-CoA synthase, adipocyte complement-related protein of 30 kDa, and transcription factors CCAAT/enhancer binding protein-alpha, receptor retinoid X receptor-alpha, and peroxisome profilerator-activated receptor gamma were significantly downregulated by TNF-alpha treatment.
93	11978627	Correspondingly, 24-h exposure of 3T3-L1 adipocytes to TNF-alpha resulted in reduced protein levels of GLUT4 and several insulin signaling proteins, including the insulin receptor, insulin receptor substrate 1 (IRS-1), and protein kinase B (AKT).
94	11978627	Nuclear factor-kappaB (NF-kappaB) was activated within 15 min of TNF-alpha addition. 3T3-L1 adipocytes expressing IkappaBalpha-DN, a nondegradable NF-kappaB inhibitor, exhibited normal morphology, global gene expression, and insulin responses.
95	11978627	However, absence of NF-kappaB activation abolished suppression of >98% of the genes normally suppressed by TNF-alpha and induction of 60-70% of the genes normally induced by TNF-alpha.
96	11978627	Moreover, extensive cell death occurred in IkappaBalpha-DN-expressing adipocytes after 2 h of TNF-alpha treatment.
97	11978627	Thus the changes in adipocyte gene expression induced by TNF-alpha could lead to insulin resistance.
98	11978627	Further, NF-kappaB is an obligatory mediator of most of these TNF-alpha responses.
99	11978627	Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory.
100	11978627	Tumor necrosis factor-alpha (TNF-alpha) is a contributing cause of the insulin resistance seen in obesity and obesity-linked type 2 diabetes, but the mechanism(s) by which TNF-alpha induces insulin resistance is not understood.
101	11978627	TNF-alpha-induced genes include transcription factors implicated in preadipocyte gene expression or NF-kappaB activation, cytokines and cytokine-induced proteins, growth factors, enzymes, and signaling molecules.
102	11978627	Importantly, a number of adipocyte-abundant genes, including GLUT4, hormone sensitive lipase, long-chain fatty acyl-CoA synthase, adipocyte complement-related protein of 30 kDa, and transcription factors CCAAT/enhancer binding protein-alpha, receptor retinoid X receptor-alpha, and peroxisome profilerator-activated receptor gamma were significantly downregulated by TNF-alpha treatment.
103	11978627	Correspondingly, 24-h exposure of 3T3-L1 adipocytes to TNF-alpha resulted in reduced protein levels of GLUT4 and several insulin signaling proteins, including the insulin receptor, insulin receptor substrate 1 (IRS-1), and protein kinase B (AKT).
104	11978627	Nuclear factor-kappaB (NF-kappaB) was activated within 15 min of TNF-alpha addition. 3T3-L1 adipocytes expressing IkappaBalpha-DN, a nondegradable NF-kappaB inhibitor, exhibited normal morphology, global gene expression, and insulin responses.
105	11978627	However, absence of NF-kappaB activation abolished suppression of >98% of the genes normally suppressed by TNF-alpha and induction of 60-70% of the genes normally induced by TNF-alpha.
106	11978627	Moreover, extensive cell death occurred in IkappaBalpha-DN-expressing adipocytes after 2 h of TNF-alpha treatment.
107	11978627	Thus the changes in adipocyte gene expression induced by TNF-alpha could lead to insulin resistance.
108	11978627	Further, NF-kappaB is an obligatory mediator of most of these TNF-alpha responses.
109	12540607	In the present study, the transcriptional regulation by cytokines of the rat MCP-1 gene in fluorescence-activated cell sorting-purified rat beta-cells, insulin-producing INS-1E cells, and RINm5F cells was investigated.
110	12540607	Blocking of NF-kappaB activation in cytokine-exposed primary beta-cells by an adenovirus overexpressing a nondegradable form of IkappaBalpha or by pyrrolidine dithiocarbamate decreased IL-1beta-induced MCP-1 mRNA expression.
111	12540607	We conclude that NF-kappaB plays an important role for MCP-1 expression in beta-cells.
112	12574341	This hyperactivation was detected for different NF-kappaB complexes and correlated with increased IkappaBalpha degradation.
113	12574341	Furthermore, increased NF-kappaB activation resulted in an enhanced capacity of NOD vs NOR or BALB/c Mphi to secrete IL-12(p70), TNF-alpha, and IL-1alpha, which was inhibited upon infection with an adenoviral recombinant encoding a modified form of IkappaBalpha.
114	12574341	In contrast, elevated NF-kappaB activation had no significant effect on the capacity of NOD Mphi to stimulate CD4(+) or CD8(+) T cells in an Ag-specific manner.
115	12706864	Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to exert potent cytotoxic activity against many tumor cells but not normal cells.
116	12706864	We found that most TRAIL-resistant and -partial resistant clones expressed low levels of DR5, whereas most TRAIL-sensitive clones expressed high levels of Death Receptor (DR5).
117	12706864	However, there were clones with a range of different TRAIL-sensitivities that had similar levels of DR5 expression.
118	12706864	The expression levels of DR4 and the decoy receptors, DcR1 and DcR2, did not correlate with TRAIL sensitivities.
119	12706864	We also compared the subgroups in terms of the expression of Fas-associated death domain protein (FADD), the levels of activation of Receptor Interacting Protein (RIP) and caspases, and cleavage of Poly (ADP-Ribose)Polymerase (PARP).
120	12706864	After treatment with TRAIL, both TRAIL-sensitive and partial resistant clones showed high levels of activation of caspase-3, caspase-8, RIP and PARP.
121	12706864	Relative basal level and induced level of Phosphoprotein over Expressed in Diabetes/Phosphoprotein Enriched in Astrocytes (PED/PEA-15) after TRAIL treatment were compared in the clones.
122	12706864	TRAIL did not change the PED/PEA-15 level in the clones.
123	12706864	In addition, transduction and expression of the dominant negative form of the I-kBalpha gene did not change TRAIL-sensitivities.
124	12706864	Our results showed that the expression levels of DR5, the activation levels of caspase-8, -3 and RIP were critical factors in determining TRAIL-sensitivities in Jurkat cells.
125	14555214	Although distinct receptors, all members share a common cell signaling pathway that mediates the activation of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (e.g. c-jun N-terminal kinase).
126	14555214	Regulation of cell growth and activation of NF-kappaB and of c-jun N-terminal kinase by the TNF super family is mediated through sequential activation/association of a set of cell signaling proteins named TNF receptor-associated factors, Fas-associated death domain and FADD-like ICE, caspases, receptor-interacting protein, NF-kappaB-inducing kinases, and IkappaBalpha kinases.
127	15294940	The inhibition of islet chemokine production in vivo persists after restimulation with TLR ligands and is associated with up-regulation of IkappaBalpha transcription, an inhibitor of NF-kappaB and with arrest of NF-kappaBp65 nuclear translocation, highlighting a novel mechanism of action exerted by vitamin D receptor ligands potentially relevant for the treatment of T1D and other autoimmune diseases.
128	15322087	Guggulsterone inhibits NF-kappaB and IkappaBalpha kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis.
129	15322087	Guggulsterone suppressed DNA binding of NF-kappaB induced by tumor necrosis factor (TNF), phorbol ester, okadaic acid, cigarette smoke condensate, hydrogen peroxide, and interleukin-1.
130	15322087	NF-kappaB-dependent reporter gene transcription induced by TNF, TNFR1, TRADD, TRAF2, NIK, and IKK was also blocked by guggulsterone but without affecting p65-mediated gene transcription.
131	15322087	In addition, guggulsterone decreased the expression of gene products involved in anti-apoptosis (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP, and survivin), proliferation (cyclin D1 and c-Myc), and metastasis (MMP-9, COX-2, and VEGF); this correlated with enhancement of apoptosis induced by TNF and chemotherapeutic agents.
132	15450943	Inhibitory effects of epicatechin on interleukin-1beta-induced inducible nitric oxide synthase expression in RINm5F cells and rat pancreatic islets by down-regulation of NF-kappaB activation.
133	15450943	Specifically, interleukin-1beta (IL-1beta) stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction, leading to the beta-cell damage.
134	15450943	IkappaBalpha protein, nuclear translocation of NF-kappaB, and NF-kappaB DNA binding activity were also determined.
135	15450943	Epicatechin significantly reduced IL-1beta-induced nitrite production, iNOS protein and mRNA expressions, and it also inhibited IL-1beta-induced IkappaBalpha protein degradation, NF-kappaB activation, and iNOS promoter activity.
136	15450943	These results suggest that epicatechin inhibits the IL-1beta-induced iNOS expression by down-regulating NF-kappaB activation, and protecting beta-cells from IL-1beta.
137	15450943	Inhibitory effects of epicatechin on interleukin-1beta-induced inducible nitric oxide synthase expression in RINm5F cells and rat pancreatic islets by down-regulation of NF-kappaB activation.
138	15450943	Specifically, interleukin-1beta (IL-1beta) stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction, leading to the beta-cell damage.
139	15450943	IkappaBalpha protein, nuclear translocation of NF-kappaB, and NF-kappaB DNA binding activity were also determined.
140	15450943	Epicatechin significantly reduced IL-1beta-induced nitrite production, iNOS protein and mRNA expressions, and it also inhibited IL-1beta-induced IkappaBalpha protein degradation, NF-kappaB activation, and iNOS promoter activity.
141	15450943	These results suggest that epicatechin inhibits the IL-1beta-induced iNOS expression by down-regulating NF-kappaB activation, and protecting beta-cells from IL-1beta.
142	15479644	IKKbeta/NF-kappaB activation causes severe muscle wasting in mice.
143	15479644	In contrast, no overt phenotype was seen upon muscle-specific inhibition of NF-kappaB through expression of IkappaBalpha superrepressor (MISR).
144	15479644	Pharmacological or genetic inhibition of the IKKbeta/NF-kappaB/MuRF1 pathway reversed muscle atrophy.
145	15561958	Postclamp liver but not muscle phosphorylated/total Akt protein was increased, whereas basal c-Jun NH2-terminal kinase-1 and -2 protein expression were reduced (by 39 and 53%, respectively; P < 0.05).
146	15561958	Metformin also increased hepatic basal IkappaBalpha levels (by 260%; P < 0.001) but had no effect on tyrosine phosphorylation or expression of insulin receptor substrate-1 (IRS-1).
147	15888549	Contraction of isolated extensor digitorum longus muscles in vitro increased IKKalpha/beta phosphorylation sevenfold and this was accompanied by a parallel increase in IkappaBalpha phosphorylation.
148	15888549	Additional kinases that are activated by exercise include p38, extracellular-signal regulated protein kinase (ERK), and AMP-activated protein kinase (AMPK).
149	15888549	Inhibitors of p38 (SB-203580) and ERK (U-0126) blunted contraction-mediated IKK phosphorylation by 39 +/- 4% (P = 0.06) and 35 +/- 10% (P = 0.09), respectively, and in combination by 76 +/- 5% (P < 0.05), suggesting that these kinases might influence the activation of IKK and NF-kappaB during exercise.
150	15888549	In contrast, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, an activator of AMPK, had no effect on either IKK or NF-kappaB activity.
151	16039994	Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway.
152	16039994	Resistin, a recently discovered 92 amino acid protein involved in the development of insulin resistance, has been associated with obesity and type 2 diabetes.
153	16039994	Addition of recombinant human resistin protein (hResistin) to macrophages (both murine and human) resulted in enhanced secretion of pro-inflammatory cytokines, TNF-alpha and IL-12, similar to that obtained using 5 microg/ml lipopolysaccharide.
154	16039994	Induction of TNF-alpha in U937 cells by hResistin was markedly reduced in the presence of either dominant negative IkappaBalpha plasmid or PDTC, a pharmacological inhibitor of NF-kappaB.
155	16177186	Quercetin decreases oxidative stress, NF-kappaB activation, and iNOS overexpression in liver of streptozotocin-induced diabetic rats.
156	16177186	Eight weeks later we measured TBARS and hydroperoxide-initiated chemiluminescence (QL) in liver as markers of oxidative stress, and activities of the antioxidant enzymes catalase, superoxide dismutase (SOD), and glutathione peroxidase, NF-kappaB activation by an electrophoretic mobility shift assay and expression of IkappaB kinases (IKKalpha and IKKbeta), the inhibitor IkappaB (IkappaBalpha and IkappaBbeta), and iNOS by Western blot.
157	16177186	Streptozotocin administration induced significant increases in hepatic TBARS concentration, QL, and SOD and catalase activities that were prevented by quercetin.
158	16177186	Activation of NF-kappaB, induction of IKKalpha and iNOS protein levels, and increased degradation of IkappaBalpha were also observed in streptozotocin-treated rats.
159	16177186	Quercetin decreases oxidative stress, NF-kappaB activation, and iNOS overexpression in liver of streptozotocin-induced diabetic rats.
160	16177186	Eight weeks later we measured TBARS and hydroperoxide-initiated chemiluminescence (QL) in liver as markers of oxidative stress, and activities of the antioxidant enzymes catalase, superoxide dismutase (SOD), and glutathione peroxidase, NF-kappaB activation by an electrophoretic mobility shift assay and expression of IkappaB kinases (IKKalpha and IKKbeta), the inhibitor IkappaB (IkappaBalpha and IkappaBbeta), and iNOS by Western blot.
161	16177186	Streptozotocin administration induced significant increases in hepatic TBARS concentration, QL, and SOD and catalase activities that were prevented by quercetin.
162	16177186	Activation of NF-kappaB, induction of IKKalpha and iNOS protein levels, and increased degradation of IkappaBalpha were also observed in streptozotocin-treated rats.
163	16210596	Additionally, preincubation decreased NF-kappaB DNA-binding activity to control levels, whereas the inhibitory protein IkappaBalpha was increased.
164	16210596	In MS patients, pioglitazone-induced increase in PPAR-gamma DNA-binding activity and decrease in NF-kappaB DNA-binding activity was only observed in the absence of an acute MS relapse.
165	16919536	Glucose ingestion (75 g in 300 mL water) in healthy human subjects resulted in an increase in intranuclear nuclear factor kappaB (NF-kappaB) binding, the reduction of inhibitor kappaB alpha (IkappaBalpha) protein, and an increase in the activity of inhibitor kappaB kinase (IKK) and the expression of IKKalpha and IKKbeta, the enzymes that phosphorylate IkappaBalpha, in MNCs.
166	16919536	Glucose intake caused an increase in NF-kappaB binding to NF-kappaB2, NF-kappaB2a, and NF-kappaB3 sequences in the promoter site of tumor necrosis factor alpha (TNF-alpha) gene along with an increase in the expression of TNF-alpha messenger RNA in MNCs.
167	16919536	Membranous p47(phox) subunit, an index of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and activation, also increased after glucose intake.
168	16919536	We conclude that glucose intake induces an immediate increase in intranuclear NF-kappaB binding, a fall in IkappaBalpha, an increase in IKKalpha, IKKbeta, IKK activity, and messenger RNA expression of TNF-alpha in MNCs in healthy subjects.
169	16919536	Glucose ingestion (75 g in 300 mL water) in healthy human subjects resulted in an increase in intranuclear nuclear factor kappaB (NF-kappaB) binding, the reduction of inhibitor kappaB alpha (IkappaBalpha) protein, and an increase in the activity of inhibitor kappaB kinase (IKK) and the expression of IKKalpha and IKKbeta, the enzymes that phosphorylate IkappaBalpha, in MNCs.
170	16919536	Glucose intake caused an increase in NF-kappaB binding to NF-kappaB2, NF-kappaB2a, and NF-kappaB3 sequences in the promoter site of tumor necrosis factor alpha (TNF-alpha) gene along with an increase in the expression of TNF-alpha messenger RNA in MNCs.
171	16919536	Membranous p47(phox) subunit, an index of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and activation, also increased after glucose intake.
172	16919536	We conclude that glucose intake induces an immediate increase in intranuclear NF-kappaB binding, a fall in IkappaBalpha, an increase in IKKalpha, IKKbeta, IKK activity, and messenger RNA expression of TNF-alpha in MNCs in healthy subjects.
173	17002901	We examined the CA repeat polymorphism of the NFKB1 gene (encoding for NFkappaB) and A/G point variation in the 3'UTR region of the nuclear factor kappa B inhibitor alpha (NFKBIA) gene (encoding for IkappaB) in Czech and German patients with type 2 diabetes.
174	17267600	To investigate the role of beta cell NF-kappaB in autoimmune diabetes, we produced transgenic mice expressing a nondegradable form of IkappaBalpha in pancreatic beta cells (RIP-mIkappaBalpha mice). beta cells of these mice were more susceptible to killing by TNF-alpha plus IFN-gamma but more resistant to IL-1beta plus IFN-gamma than normal beta cells.
175	17267600	Inhibition of beta cell NF-kappaB accelerated the development of autoimmune diabetes in nonobese diabetic mice but had no effect on glucose tolerance or serum insulin in C57BL/6 mice, precluding a nonphysiological effect of transgene expression.
176	17267600	These results suggest that under conditions that resemble autoimmune type 1 diabetes, the dominant effect of NF-kappaB is prevention of TNF-induced apoptosis.
177	17273805	Cytokines stimulate an inducible form of nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, leading to insulin insufficiency.
178	17273805	Treatment of RINm5F (RIN) rat insulinoma cells with interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) induced cell damage.
179	17273805	ACE completely protected IL-1beta and IFN-gamma-mediated cytotoxicity in a concentration-dependent manner.
180	17273805	Incubation with ACE resulted in a significant reduction in IL-1beta and IFN-gamma-induced NO production, a finding that correlated well with reduced levels of the iNOS mRNA and protein.
181	17273805	The molecular mechanism by which ACE inhibited iNOS gene expression appeared to involve the inhibition of NF-kappaB activation.
182	17273805	The IL-1beta and IFN-gamma-stimulated RIN cells showed increases in NF-kappaB binding activity and p65 subunit levels in the nucleus, and IkappaBalpha degradation in cytosol compared to unstimulated cells.
183	17273805	Furthermore, ACE restored the cytokine-induced inhibition of insulin release from isolated islets.
184	17273805	These results suggest that ACE protects beta-cells by suppressing NF-kappaB activation.
185	17318773	HLA, NFKB1 and NFKBIA gene polymorphism profile in autoimmune diabetes mellitus patients.
186	17318773	The triggering of the autoimmune process has been ascribed to various genes active in the regulation of the cytokine gene transcription including the Rel/NF-kappaB gene family.
187	17318773	In our study the gene polymorphism of HLA class II, NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and NFKBIA (inhibitor of nuclear factor kappa B) was tested.
188	17318773	HLA-DRB1 ()04 and HLA-DQB1 ()0302 have been detected as risk factors for T1DM in adults and particularly in children (P<0.0001, OR=22.9 and 46.5 respectively).
189	17318773	Summarizing our results we concluded that there is a high probability of association of gene polymorphism from Rel/NF-kappaB family with an autoimmune diabetes course.
190	17318773	No significant changes have been observed by real time PCR testing of HLA-DRB1 (*)04 gene and NFKB1 gene expression between T1DM diabetic group with different HLA, NFKB1, NFKBIA genetic background.
191	17318773	HLA, NFKB1 and NFKBIA gene polymorphism profile in autoimmune diabetes mellitus patients.
192	17318773	The triggering of the autoimmune process has been ascribed to various genes active in the regulation of the cytokine gene transcription including the Rel/NF-kappaB gene family.
193	17318773	In our study the gene polymorphism of HLA class II, NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and NFKBIA (inhibitor of nuclear factor kappa B) was tested.
194	17318773	HLA-DRB1 ()04 and HLA-DQB1 ()0302 have been detected as risk factors for T1DM in adults and particularly in children (P<0.0001, OR=22.9 and 46.5 respectively).
195	17318773	Summarizing our results we concluded that there is a high probability of association of gene polymorphism from Rel/NF-kappaB family with an autoimmune diabetes course.
196	17318773	No significant changes have been observed by real time PCR testing of HLA-DRB1 (*)04 gene and NFKB1 gene expression between T1DM diabetic group with different HLA, NFKB1, NFKBIA genetic background.
197	17318773	HLA, NFKB1 and NFKBIA gene polymorphism profile in autoimmune diabetes mellitus patients.
198	17318773	The triggering of the autoimmune process has been ascribed to various genes active in the regulation of the cytokine gene transcription including the Rel/NF-kappaB gene family.
199	17318773	In our study the gene polymorphism of HLA class II, NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and NFKBIA (inhibitor of nuclear factor kappa B) was tested.
200	17318773	HLA-DRB1 ()04 and HLA-DQB1 ()0302 have been detected as risk factors for T1DM in adults and particularly in children (P<0.0001, OR=22.9 and 46.5 respectively).
201	17318773	Summarizing our results we concluded that there is a high probability of association of gene polymorphism from Rel/NF-kappaB family with an autoimmune diabetes course.
202	17318773	No significant changes have been observed by real time PCR testing of HLA-DRB1 (*)04 gene and NFKB1 gene expression between T1DM diabetic group with different HLA, NFKB1, NFKBIA genetic background.
203	17507908	1,25-Dihydroxyvitamin D3 targeting of NF-kappaB suppresses high glucose-induced MCP-1 expression in mesangial cells.
204	17507908	Electrophoretic mobility shift and chromatin immunoprecipitation assays showed that HG increased the p65/p50 binding to the two NF-kappaB sites within the promoter.
205	17507908	This was suppressed by 1,25(OH)2D3, but this decrease was reversed by overexpression of p65. 1,25(OH)2D3 was found to stabilize IkappaBalpha leading to an inhibition of p65 translocation to the nucleus and subsequent reduction of NF-kappaB binding.
206	17507908	In primary MCs prepared from vitamin D receptor knockout animals, basal MCP-1 levels were elevated but not affected by 1,25(OH)2D3.
207	17701919	NFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases.
208	17701919	In this review, we focus on polymorphisms of the NFKB and NFKBI genes in relation to development of common inflammatory diseases including ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, giant cell arthritis, type 1 diabetes, multiple sclerosis, celiac disease, and Parkinson's disease, as well as susceptibility of several cancers, such as oral squamous cell carcinoma, colorectal cancer (CRC), hepatocellular carcinoma, breast cancer and myeloma.
209	17701919	NFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases.
210	17701919	In this review, we focus on polymorphisms of the NFKB and NFKBI genes in relation to development of common inflammatory diseases including ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, giant cell arthritis, type 1 diabetes, multiple sclerosis, celiac disease, and Parkinson's disease, as well as susceptibility of several cancers, such as oral squamous cell carcinoma, colorectal cancer (CRC), hepatocellular carcinoma, breast cancer and myeloma.
211	17912472	However, treatment of RIN cells with RAE protected the IL-1beta and IFN-gamma- mediated viability and proliferation reduction in a concentration-dependent manner.
212	17912472	Incubation with RAE also resulted in significant suppression of IL-1beta and IFN-gamma-induced nitric oxide (NO) production, and this reduction was correlated with reduced levels of mRNA and protein associated with the inducible form of NO synthase (iNOS).
213	17912472	The molecular mechanism by which RAE inhibited iNOS gene expression appeared to involve the inhibition of NF-kappaB activation as a result of RAE's suppression of IL-1beta and IFN-gamma-induced IkappaBalpha degradation.
214	17912472	The protective effects of RAE were verified via the observation of reduced NO generation and iNOS expression, as well as the observation of normal insulin-secretion responses to glucose in IL-1beta and IFN-gamma-treated rat islets.
215	18346469	Increase in P-glycoprotein accompanied by activation of protein kinase Calpha and NF-kappaB p65 in the livers of rats with streptozotocin-induced diabetes.
216	18346469	It is known that protein kinase C (PKC) signal transduction is enhanced in a diabetic state, and that PKC activator phorbol esters increase the gene expression of MDR1 in human tumor cells.
217	18346469	To clarify the expression of the liver transporters under diabetic conditions and the roles of PKCalpha and the transcription factor NF-kappaB, we investigated the expression levels of Mdr1a, Mdr1b, Mdr2, Mrp2, Bcrp, Bsep, Oct1, Oat2, and Oat3 transporters, PKCalpha, IkappaB, and NF-kappaB in the liver of rats with STZ-induced hyperglycemia.
218	18346469	NF-kappaB p65, IkappaBalpha and IkappaBbeta mRNA levels were increased as was the level of nuclear NF-kappaB p65.
219	18346469	From these findings, it was suggested that STZ-induced hyperglycemia caused the upregulation of Mdr1b P-gp expression through the activation of PKCalpha and NF-kappaB.
220	18423412	Inhibition of NADPH oxidase-related oxidative stress-triggered signaling by honokiol suppresses high glucose-induced human endothelial cell apoptosis.
221	18423412	Here we explored the efficacy of honokiol, a small molecular weight natural product, on NADPH oxidase-related oxidative stress-mediated NF-kappaB-regulated signaling and apoptosis in human umbilical vein endothelial cells (HUVECs) under hyperglycemic conditions.
222	18423412	Submicromolar concentrations of honokiol suppressed the increases of NADPH oxidase activity, Rac-1 phosphorylation, p22(phox) protein expression, and reactive oxygen species production in high glucose (HG)-stimulated HUVECs.
223	18423412	The degradation of IkappaBalpha and increase of NF-kappaB activity were inhibited by honokiol in HG-treated HUVECs.
224	18423412	Moreover, honokiol (0.125-1 microM) also suppressed HG-induced cyclooxygenase (COX)-2 upregulation and prostaglandin E(2) production in HUVECs.
225	18423412	These results imply that inhibition of NADPH oxidase-related oxidative stress by honokiol suppresses the HG-induced NF-kappaB-regulated COX-2 upregulation, apoptosis, and cell death in HUVECs, which has the potential to be developed as a therapeutic agent to prevent hyperglycemia-induced endothelial damage.
226	18827362	Troglitazone increases IL-1beta induced cyclooxygenase-2 and inducible nitric oxide synthase expression via enhanced phosphorylation of IkappaBalpha in vascular smooth muscle cells from Wistar-Kyoto rats and spontaneously hypertensive rats.
227	18827362	Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists of the thiazolidinedione class are widely used for the treatment of type 2 diabetes subjects due to their ability to improve insulin resistance.
228	18827362	We report here that troglitazone but not ciglitazone increased IL-1beta induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in vascular smooth muscle cell (VSMC) from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR).
229	18827362	Potentiated expression of COX-2 and iNOS by troglitazone was inhibited by MG-132, a specific inhibitor of inhibitory factor kappaB (IkappaB) activation.
230	18827362	Troglitazone treatment of these cells also resulted in a dose-dependent increase in IL-1beta induced IkappaBalpha phosphorylation.
231	18827362	These data suggest that troglitazone is capable of increasing IL-1beta induced COX-2 and iNOS expression through an IkappaBalpha dependent mechanism in VSMC from WKY and SHR.
232	18827362	Troglitazone increases IL-1beta induced cyclooxygenase-2 and inducible nitric oxide synthase expression via enhanced phosphorylation of IkappaBalpha in vascular smooth muscle cells from Wistar-Kyoto rats and spontaneously hypertensive rats.
233	18827362	Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists of the thiazolidinedione class are widely used for the treatment of type 2 diabetes subjects due to their ability to improve insulin resistance.
234	18827362	We report here that troglitazone but not ciglitazone increased IL-1beta induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in vascular smooth muscle cell (VSMC) from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR).
235	18827362	Potentiated expression of COX-2 and iNOS by troglitazone was inhibited by MG-132, a specific inhibitor of inhibitory factor kappaB (IkappaB) activation.
236	18827362	Troglitazone treatment of these cells also resulted in a dose-dependent increase in IL-1beta induced IkappaBalpha phosphorylation.
237	18827362	These data suggest that troglitazone is capable of increasing IL-1beta induced COX-2 and iNOS expression through an IkappaBalpha dependent mechanism in VSMC from WKY and SHR.
238	18827362	Troglitazone increases IL-1beta induced cyclooxygenase-2 and inducible nitric oxide synthase expression via enhanced phosphorylation of IkappaBalpha in vascular smooth muscle cells from Wistar-Kyoto rats and spontaneously hypertensive rats.
239	18827362	Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists of the thiazolidinedione class are widely used for the treatment of type 2 diabetes subjects due to their ability to improve insulin resistance.
240	18827362	We report here that troglitazone but not ciglitazone increased IL-1beta induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in vascular smooth muscle cell (VSMC) from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR).
241	18827362	Potentiated expression of COX-2 and iNOS by troglitazone was inhibited by MG-132, a specific inhibitor of inhibitory factor kappaB (IkappaB) activation.
242	18827362	Troglitazone treatment of these cells also resulted in a dose-dependent increase in IL-1beta induced IkappaBalpha phosphorylation.
243	18827362	These data suggest that troglitazone is capable of increasing IL-1beta induced COX-2 and iNOS expression through an IkappaBalpha dependent mechanism in VSMC from WKY and SHR.
244	19288032	Interleukin (IL)-1beta and interferon (IFN)-gamma are the primary cytokines responsible for stimulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction, which leads to beta-cell damage.
245	19288032	In this study, the effects of Fructus Xanthii extract (FXE) on IL-1beta and IFN-gamma-induced beta-cell damage were examined.
246	19288032	Treatment of RINm5F cells with IL-1beta and IFN-gamma reduced cell viability, however, FXE completely protected cells from IL-1beta and IFN-gamma-mediated reduction in viability in a concentration-dependent manner.
247	19288032	In addition, incubation with FXE resulted in a significant suppression of IL-1beta and IFN-gamma-induced nitric oxide (NO) production, which correlated with the reduced levels of the inducible form of iNOS mRNA and protein observed.
248	19288032	The IL-1beta and IFN-gamma-stimulated RIN cells showed increases in NF-kappaB binding activity and p50 subunit levels in the nucleus, as well as increased IkappaBalpha degradation in cytosol when compared to unstimulated cells, which indicates that the mechanism by which FXE inhibited the iNOS gene involves inhibition of NF-kappaB activation.
249	19288032	Furthermore, a protective effect of FXE was demonstrated by reduction in NO generation and iNOS expression, as well as the normal insulin secreting responses to glucose observed in IL-1beta and IFN-gamma-treated islets.
250	19569009	Recently, a link between obesity and insulin resistance has been established via IKKbeta action and IRS-1 Ser (312/307) phosphorylation.
251	19569009	This study measured IkappaBalpha and IRS-1 pSer (307) in mixed gastrocnemius muscle in HCR and LCR rats challenged with a 12-wk HFD.
252	19569009	IkappaBalpha levels, an inverse indicator of IKKbeta activity, were lower in LCR vs.
253	19569009	Recently, a link between obesity and insulin resistance has been established via IKKbeta action and IRS-1 Ser (312/307) phosphorylation.
254	19569009	This study measured IkappaBalpha and IRS-1 pSer (307) in mixed gastrocnemius muscle in HCR and LCR rats challenged with a 12-wk HFD.
255	19569009	IkappaBalpha levels, an inverse indicator of IKKbeta activity, were lower in LCR vs.
256	20004646	Tumor necrosis factor-alpha increases alkaline phosphatase expression in vascular smooth muscle cells via MSX2 induction.
257	20004646	TNF-alpha increased the expression of osteogenic marker genes including RUNX2, osterix, alkaline phosphatase (ALP), and bone sialoprotein, and it also promoted matrix mineralization in VSMCs.
258	20004646	In addition, TNF-alpha enhanced MSX2 expression in a dose- and time-dependent manner.
259	20004646	MSX2 over-expression alone induced ALP expression, whereas knockdown of MSX2 with small interfering RNA completely blocked TNF-alpha-induced ALP expression.
260	20004646	New protein synthesis was dispensable for MSX2 induction by TNF-alpha, and the inhibition of NF-kappaB by BAY-11-7082 or by dominant negative IkappaBalpha abolished the TNF-alpha-directed induction of MSX2 expression.
261	20004646	In conclusion, our study suggests that TNF-alpha directly induces MSX2 expression through the NF-kappaB pathway, which in turn induces expression of ALP, a key molecule in mineralization, in VSMCs.
262	20053369	STZ administration elevated the levels of IL-2 as well as IFN-gamma and attenuated the level of TNF-alpha in the sera of diabetic animals.
263	20053369	Investigating the oxidative stress responsive cell signaling pathways, increased expressions (immunoreactive concentrations) of phosphorylated p65 as well as its inhibitor protein phospho IkappaBalpha and phosphorylated mitogen activated protein kinases (MAPKs) have been observed in diabetic spleen tissue.
264	20053369	Studies on isolated splenocytes revealed that hyperglycemia caused disruption of mitochondrial membrane potential, elevation in the concentration of cytosolic cytochrome c as well as activation of caspase 3 leading to apoptotic cell death.
265	20354158	Hypothalamic inflammation induced by high-fat feeding causes insulin and leptin resistance and contributes to the pathogenesis of obesity.
266	20354158	Insulin-treated cells were evaluated for induction of markers of insulin receptor signaling (p-IRS, p-Akt).
267	20354158	In both hypothalamic cell lines, inflammation was induced by prototypical inflammatory mediators LPS and TNFalpha, as judged by induction of IkappaBalpha (3- to 5-fold) and IL-6 (3- to 7-fold) mRNA and p-IkappaBalpha protein, and TNFalpha pretreatment reduced insulin-mediated p-Akt activation by 30% (P < 0.05).
268	20393162	Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment.
269	20393162	Additionally, given that AMPK-activating drugs are widely prescribed for their insulin-sensitizing effects, we sought to determine whether 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR)-stimulated AMPK activation could prevent or reverse the deleterious effects of lipid on insulin signaling.
270	20393162	We found that a 1-h palmitate incubation in lean myotubes reduced (P < 0.05) insulin-stimulated phosphoprotein kinase B (Akt), Akt substrate 160 (AS160), and inhibitory factor kappaBalpha (IkappaBalpha) mass, all of which were prevented with AICAR inclusion.
271	20393162	With a longer incubation, we observed that myotubes from morbidly obese individuals appear to be largely resistant to the detrimental effects of 16 h lipid exposure as was evident, in contrast to the lean, by the absence of a reduction in insulin-stimulated insulin receptor substrate (IRS)-1 Tyr phosphorylation, phospho-Akt, and phospho-AS160 (P < 0.05).
272	20393162	Furthermore, 16 h lipid exposure significantly reduced IkappaBalpha levels and increased phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and IRS1-Ser(312) in lean myotubes only (P < 0.05).
273	20393162	Despite a divergent response to lipid between lean and obese myotubes, AICAR inclusion improved insulin signaling in all myotubes.
274	20393162	Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment.
275	20393162	Additionally, given that AMPK-activating drugs are widely prescribed for their insulin-sensitizing effects, we sought to determine whether 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR)-stimulated AMPK activation could prevent or reverse the deleterious effects of lipid on insulin signaling.
276	20393162	We found that a 1-h palmitate incubation in lean myotubes reduced (P < 0.05) insulin-stimulated phosphoprotein kinase B (Akt), Akt substrate 160 (AS160), and inhibitory factor kappaBalpha (IkappaBalpha) mass, all of which were prevented with AICAR inclusion.
277	20393162	With a longer incubation, we observed that myotubes from morbidly obese individuals appear to be largely resistant to the detrimental effects of 16 h lipid exposure as was evident, in contrast to the lean, by the absence of a reduction in insulin-stimulated insulin receptor substrate (IRS)-1 Tyr phosphorylation, phospho-Akt, and phospho-AS160 (P < 0.05).
278	20393162	Furthermore, 16 h lipid exposure significantly reduced IkappaBalpha levels and increased phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and IRS1-Ser(312) in lean myotubes only (P < 0.05).
279	20393162	Despite a divergent response to lipid between lean and obese myotubes, AICAR inclusion improved insulin signaling in all myotubes.
280	20451496	TRAIL upregulates decoy receptor 1 and mediates resistance to apoptosis in insulin-secreting INS-1 cells.
281	20451496	TRAIL/Apo2L (tumor necrosis factor-related apoptosis-inducing ligand) is a multifunctional protein regulating the homeostasis of the immune system, infection, autoimmune diseases, and apoptosis.
282	20451496	A previous study found that TRAIL did not have significant cytotoxic effects on the insulin-secreting pancreatic beta cell line, INS-1.
283	20451496	TRAIL treatment showed NF-kappaB translocation to the nucleus in TRAIL-resistant INS-1 cells, and TRAIL-induced NF-kappaB activation was preceded by IkappaBalpha degradation.
284	20451496	A pharmacological inhibitor of NF-kappaB, Bay 11-7082, blocked TRAIL-induced NF-kappaB translocation to the nucleus and IkappaBalpha degradation.
285	20451496	Four related receptors bind TRAIL: two death receptors (DR4 and DR5) that promote apoptosis, and two decoy receptors (DcR1 and DcR2) that act as dominant-negative inhibitors of TRAIL-mediated apoptosis.
286	20451496	In the present study, TRAIL treatment in INS-1 cells upregulated DcR1 and downregulated DR5 without altering the expression of DcR2 and DR4.
287	20451496	The resistance to apoptosis in INS-1 cells might therefore, be a consequence of DcR1 upregulation and DR5 downregulation, and the transcription factor, NF-kappaB, could regulate the sensitivity of cells to TRAIL by controlling the ratio of decoy to death receptors.
288	20451496	Thus, TRAIL may play an important role in the survival of pancreatic beta cells by regulating receptor expression in an NF-kappaB-dependent manner.
289	20451496	TRAIL upregulates decoy receptor 1 and mediates resistance to apoptosis in insulin-secreting INS-1 cells.
290	20451496	TRAIL/Apo2L (tumor necrosis factor-related apoptosis-inducing ligand) is a multifunctional protein regulating the homeostasis of the immune system, infection, autoimmune diseases, and apoptosis.
291	20451496	A previous study found that TRAIL did not have significant cytotoxic effects on the insulin-secreting pancreatic beta cell line, INS-1.
292	20451496	TRAIL treatment showed NF-kappaB translocation to the nucleus in TRAIL-resistant INS-1 cells, and TRAIL-induced NF-kappaB activation was preceded by IkappaBalpha degradation.
293	20451496	A pharmacological inhibitor of NF-kappaB, Bay 11-7082, blocked TRAIL-induced NF-kappaB translocation to the nucleus and IkappaBalpha degradation.
294	20451496	Four related receptors bind TRAIL: two death receptors (DR4 and DR5) that promote apoptosis, and two decoy receptors (DcR1 and DcR2) that act as dominant-negative inhibitors of TRAIL-mediated apoptosis.
295	20451496	In the present study, TRAIL treatment in INS-1 cells upregulated DcR1 and downregulated DR5 without altering the expression of DcR2 and DR4.
296	20451496	The resistance to apoptosis in INS-1 cells might therefore, be a consequence of DcR1 upregulation and DR5 downregulation, and the transcription factor, NF-kappaB, could regulate the sensitivity of cells to TRAIL by controlling the ratio of decoy to death receptors.
297	20451496	Thus, TRAIL may play an important role in the survival of pancreatic beta cells by regulating receptor expression in an NF-kappaB-dependent manner.
298	20599720	Pharmacologic experiments suggested that TRPV family members, but neither TRPC nor TRPM family members, are involved in the LPS-induced TNFalpha and IL-6 production in RAW264 macrophages.
299	20599720	ShRNA against TRPV2 inhibited the LPS-induced TNFalpha and IL-6 production as well as IkappaBalpha degradation.
300	20599720	BAPTA/AM abolished LPS-induced TNFalpha and IL-6 production, while EGTA only partially suppressed LPS-induced IL-6 production, but not TNFalpha production.
301	20599720	In addition to Ca2+ mobilization through the IP3-receptor, TRPV2-mediated intracellular Ca2+ mobilization is involved in NFkappaB-dependent TNFalpha and IL-6 expression, while extracellular Ca2+ entry is involved in NFkappaB-independent IL-6 production.
302	20798864	Metformin Improves Insulin Signaling in Obese Rats via Reduced IKKbeta Action in a Fiber-Type Specific Manner.
303	20798864	The aim of this study was to (1) determine the ability of metformin to attenuate IKKbeta action, (2) determine whether changes in AMPK activity are associated with changes in IKKbeta action in skeletal muscle, and (3) examine whether changes in AMPK and IKKbeta function are consistent with improved insulin signaling.
304	20798864	Further, metformin increased IkappaBalpha levels in both WG (150%) and RG (67%) of obese rats, indicative of reduced IKKbeta activity (P < .05), and was associated with reduced IRS1-pSer(307) (30%) in the WG of obese rats (P < .02).
305	20798864	From these data we conclude that metformin treatment appears to exert an inhibitory influence on skeletal muscle IKKbeta activity, as evidenced by elevated IkappaBalpha levels and reduced IRS1-Ser(307) phosphorylation in a fiber-type specific manner.
306	20798864	Metformin Improves Insulin Signaling in Obese Rats via Reduced IKKbeta Action in a Fiber-Type Specific Manner.
307	20798864	The aim of this study was to (1) determine the ability of metformin to attenuate IKKbeta action, (2) determine whether changes in AMPK activity are associated with changes in IKKbeta action in skeletal muscle, and (3) examine whether changes in AMPK and IKKbeta function are consistent with improved insulin signaling.
308	20798864	Further, metformin increased IkappaBalpha levels in both WG (150%) and RG (67%) of obese rats, indicative of reduced IKKbeta activity (P < .05), and was associated with reduced IRS1-pSer(307) (30%) in the WG of obese rats (P < .02).
309	20798864	From these data we conclude that metformin treatment appears to exert an inhibitory influence on skeletal muscle IKKbeta activity, as evidenced by elevated IkappaBalpha levels and reduced IRS1-Ser(307) phosphorylation in a fiber-type specific manner.
310	22790776	The effects of chromium picolinate and chromium histidinate administration on NF-κB and Nrf2/HO-1 pathway in the brain of diabetic rats.
311	22790776	The objective of this experiment was to investigate the effects of supplemental chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB p65) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in diabetic rat brain.
312	22790776	Diabetes was associated with increases in cerebral NF-κB and 4-hydroxynonenal (4-HNE) protein adducts and decreased in cerebral nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα) and Nrf2 levels.
313	23897274	We identified the missense variant rs2303138 (p.Ala763Thr) within the LNPEP gene associated with psoriasis (Pcombined=1.83 × 10(-13), odds ratio=1.16) and validated four previously reported genes: IL28RA, NFKBIA, TRAF3IP2, and CARD14 (9.74 × 10(-11)P9.37 × 10(-5)), which confirmed the involvement of the nuclear factor-κB signaling pathway in psoriasis pathogenesis.
314	23897274	LNPEP, also named insulin-responsive aminopeptidase, was identified as an angiotensin IV receptor.
315	23897274	Pathway analysis indicated that LNPEP was involved in the renin-angiotensin system, which also has a key role in cardiovascular disease and diabetes.
316	23982206	Activation of the transcriptional function of the NF-κB protein c-Rel by O-GlcNAc glycosylation.
317	23982206	Blocking the O-GlcNAcylation of this residue abrogated c-Rel-mediated expression of the cytokine-encoding genes IL2, IFNG, and CSF2 in response to T cell receptor (TCR) activation, whereas increasing the extent of O-GlcNAcylation of cellular proteins enhanced the expression of these genes.
318	23982206	TCR- or tumor necrosis factor (TNF)-induced expression of other NF-κB target genes, such as NFKBIA (which encodes IκBα) and TNFAIP3 (which encodes A20), occurred independently of the O-GlcNAcylation of c-Rel.