Ignet

Gene Information

Gene symbol: IL1RAPL2

Gene name: interleukin 1 receptor accessory protein-like 2

HGNC ID: 5997

Synonyms: IL-1R9, TIGIRR-1, IL1RAPL-2, IL1R9

Related Genes

#	Gene Symbol	Number of hits
1	ADIPOQ	1 hits
2	CCL2	1 hits
3	CD40	1 hits
4	CD40LG	1 hits
5	CRP	1 hits
6	CXCL10	1 hits
7	IDDM2	1 hits
8	IFNG	1 hits
9	IL10	1 hits
10	IL1A	1 hits
11	IL1B	1 hits
12	IL1R1	1 hits
13	IL1R2	1 hits
14	IL1RAP	1 hits
15	IL1RL1	1 hits
16	IL1RN	1 hits
17	IL3	1 hits
18	IL4	1 hits
19	IL6	1 hits
20	IL8	1 hits
21	INDO	1 hits
22	INS	1 hits
23	IRAK1	1 hits
24	IRF3	1 hits
25	LEP	1 hits
26	LGALS1	1 hits
27	LGALS2	1 hits
28	LGALS3	1 hits
29	MYD88	1 hits
30	NEUROD1	1 hits
31	NOS1	1 hits
32	NOS2A	1 hits
33	PDX1	1 hits
34	PIK3CA	1 hits
35	PLK1	1 hits
36	PPARA	1 hits
37	RETN	1 hits
38	SERPINA1	1 hits
39	SERPINE1	1 hits
40	SOD2	1 hits
41	STAT3	1 hits
42	TGFA	1 hits
43	TGFB1	1 hits
44	TICAM1	1 hits
45	TLR4	1 hits
46	TNF	1 hits
47	VDR	1 hits

Related Sentences

#	PMID	Sentence
1	1320950	Interleukin-1 and tumor necrosis factor: effector cytokines in autoimmune diseases.
2	1320950	Although the immune response is responsible for the initiation of autoimmune diseases, the effectors of the disease process likely involves cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF).
3	1320950	Blocking IL-1 with its naturally occurring receptor antagonist, the IL-1 receptor antagonist reduces the severity of disease in animal models of inflammation and autoimmune processes.
4	1320950	Clinical studies with the IL-1 receptor antagonist will define the role for this cytokine in the pathogenesis of autoimmune diseases such as arthritis, inflammatory bowel disease, type I diabetes and vasculitis.
5	1320950	Interleukin-1 and tumor necrosis factor: effector cytokines in autoimmune diseases.
6	1320950	Although the immune response is responsible for the initiation of autoimmune diseases, the effectors of the disease process likely involves cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF).
7	1320950	Blocking IL-1 with its naturally occurring receptor antagonist, the IL-1 receptor antagonist reduces the severity of disease in animal models of inflammation and autoimmune processes.
8	1320950	Clinical studies with the IL-1 receptor antagonist will define the role for this cytokine in the pathogenesis of autoimmune diseases such as arthritis, inflammatory bowel disease, type I diabetes and vasculitis.
9	1533718	Blocking IL-1 using the IL-1 receptor antagonist has reduced the severity of disease in animal models of septic shock, diabetes, graft-vs-host disease, inflammatory bowel disease, and the spontaneous proliferation of leukemia cells.
10	1838480	Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro.
11	1838480	Clinical and experimental evidence suggests that shock, arthritis, osteoporosis, colitis, leukemia, diabetes, wasting and atherosclerosis are mediated, in part, by interleukin 1 (IL-1).
12	1838480	A naturally-occurring IL-1 inhibitor (IL-1 receptor antagonist, IL-1ra) that blocks binding of IL-1 to its receptors has been cloned and produced in recombinant organisms.
13	2001363	Analysis of the mutational data on IL-1 beta in the light of the three-dimensional structure suggests the presence of three distinct binding sites for the IL-1 receptor on the surface of the protein.
14	2001363	It is suggested that each of the three immunoglobulin domains which comprise the extracellular portion of the IL-1 receptor recognizes one of these sites.
15	2001363	Analysis of the mutational data on IL-1 beta in the light of the three-dimensional structure suggests the presence of three distinct binding sites for the IL-1 receptor on the surface of the protein.
16	2001363	It is suggested that each of the three immunoglobulin domains which comprise the extracellular portion of the IL-1 receptor recognizes one of these sites.
17	7530759	Intraislet release of interleukin 1 inhibits beta cell function by inducing beta cell expression of inducible nitric oxide synthase.
18	7530759	In this study we have evaluated the hypothesis that local release of the cytokine interleukin 1 (IL-1) by nonendocrine cells of the islet induce the expression of inducible nitric oxide synthase (iNOS) by beta cells which results in the inhibition of beta cell function.
19	7530759	Treatment of rat islets with a combination of tumor necrosis factor (TNF) and lipopolysaccharide (LPS), conditions known to activate macrophages, stimulate the expression of iNOS and the formation of nitrite.
20	7530759	Although TNF+LPS induce iNOS expression and inhibit insulin secretion by intact islets, this combination does not induce the expression of iNOS by beta or alpha cells purified by fluorescence activated cell sorting (Facs).
21	7530759	In contrast, IL-1 beta induces the expression of iNOS and also inhibits insulin secretion by both intact islets and Facs-purified beta cells, whereas TNF+LPS have no inhibitory effects on insulin secretion by purified beta cells.
22	7530759	Evidence suggests that TNF+LPS inhibit insulin secretion from islets by stimulating the release of IL-1 which subsequently induces the expression of iNOS by beta cells.
23	7530759	The IL-1 receptor antagonist protein completely prevents TNF+LPS-induced inhibition of insulin secretion and attenuates nitrite formation from islets, and neutralization of IL-1 with antisera specific for IL-1 alpha and IL-1 beta attenuates TNF+LPS-induced nitrite formation by islets.
24	7530759	Immunohistochemical localization of iNOS and insulin confirm that TNF+LPS induce the expression of iNOS by islet beta cells, and that a small percentage of noninsulin-containing cells also express iNOS.
25	7530759	Local release of IL-1 within islets appears to be required for TNF+LPS-induced inhibition of insulin secretion because TNF+LPS do not stimulate nitrite formation from islets physically separated into individual cells.
26	7530759	These findings provide the first evidence that a limited number of nonendocrine cells can release sufficient quantities of IL-1 in islets to induce iNOS expression and inhibit the function of the beta cell, which is selectively destroyed during the development of autoimmune diabetes.
27	7578987	PCR analysis of interleukin-1 receptor gene in the nonobese diabetic mouse.
28	7578987	Insulin-dependent diabetes mellitus (IDDM) is characterized by a progressive autoimmune destruction of pancreatic beta cells.
29	7578987	Many data suggest that interleukin 1 (IL-1) plays a fundamental role in the pathogenesis of the disease.
30	7578987	In the nonobese diabetic (NOD) mouse, a spontaneous model of IDDM, it was put forward that the disease is linked to a susceptibility locus, called idd5, which contains the IL-1 receptor (IL-1R) gene.
31	7578987	Using primers to amplify the IL-1R gene between bp-106 and +378, a 580 bp fragment was obtained from C57BL/6 DNA but not from DBA/2 and NOD DNA.
32	7578987	However, amplification of the IL-1R gene region between bp +1 and +378 in the three strains yielded amplicons 480 bp long.
33	7605869	The markers included MHC class I, II and III loci, the manganese superoxide dismutase (MnSOD) locus (chr. 6q), interleukin-1 beta (IL1B), the IL-1 receptor antagonist (IL1RN), and the IL-1 type 1 receptor (IL1RI) loci (each chr. 2q).
34	7605869	No significant differences between familial and sporadic cases were found within the MHC region (including the following loci: HLA-DQ, -DR, heat shock protein (HSP) 70, tumour necrosis factor (TNF), HLA-B and -A).
35	7605869	For the IL1B RFLP a trend for difference was observed between familial cases and control subjects (p = 0.046), whereas no differences between sporadic cases and control subjects could be demonstrated neither at the IL1B nor at the IL1RN loci.
36	7926295	Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) have been implicated as immune effector molecules in the pathogenesis of insulin-dependent diabetes mellitus (IDDM).
37	7926295	Recently, an increased frequency of the A1/A1 genotype of an IL-1 receptor antagonist (IL-1Ra) gene polymorphism was observed in patients with IDDM.
38	7926295	Therefore, we investigated plasma IL-1Ra and soluble TNF p55 receptor (TNFsRp55) levels in 18 men with recent-onset IDDM, 10 men with long-standing IDDM, and 35 age-matched healthy men.
39	7926295	However, when the plasma IL-1Ra levels in the subjects with IDDM and the control subjects were analyzed according to IL-1Ra genotypes, we found a 30% lower level of plasma IL-1Ra in subjects with IDDM carrying the A1/A1 genotype compared with the levels in those carrying the A1/A2 genotype (372 +/- 40 vs. 530 +/- 54 ng/l, respectively, P = 0.025).
40	8452815	While multilineage erythromyeloid progenitor cells (day 12 CFU-S) are normal in number in NOD mice, more differentiated myeloid progenitors are deficient in their in vitro responses to IL-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), and IL-5.
41	8452815	Since the diabetes-predisposing Idd-5 gene of NOD mice maps close to the IL-1 receptor, we tested NOD bone marrow cells for a defect in synergy between IL-1 and IL-3; no defect was found.
42	8608164	Inflammatory cytokines may participate in the destruction of pancreatic islets during the pathogenesis of insulin-dependent diabetes mellitus, and the cytokine interleukin-1 (IL-1) strongly inhibits insulin secretion from rat pancreatic islets by a process which involves induction of expression of the inducible isoform of nitric oxide synthase and the overproduction of nitric oxide.
43	8608164	The signaling events between IL-1 receptor occupancy and induction of nitric oxide synthase in rat islets involve activation of the transcriptional activator NFkappa B.
44	8608164	Neither interleukin-1 nor tumor necrosis factor-alpha was found to induce hydrolysis of islet sphingomyelin species, and neither an exogenous, cell-permeant ceramide species (N-acetyl-D-sphingosine) nor exogenous sphingomyelinase mimicked or potentiated the effect of IL-1 to increase rat islet nitric oxide generation, as reflected by nitrite production.
45	8657631	The paper presents the molecular biology and biological activity of IL-1 alpha, IL-1 beta and IL-1 receptor antagonist.
46	8657631	Potential therapeutic value of IL-1 and IL-1 receptor antagonist is also discussed.
47	8657631	The paper presents the molecular biology and biological activity of IL-1 alpha, IL-1 beta and IL-1 receptor antagonist.
48	8657631	Potential therapeutic value of IL-1 and IL-1 receptor antagonist is also discussed.
49	8746789	Recombinant human transforming growth factor beta does not inhibit the effects of interleukin-1 beta on pancreatic islet cells.
50	8746789	The macrophage-derived cytokine, interleukin-1 beta (IL-1 beta), has been implicated to play an important role in the autoimmune beta cell lesion of insulin-dependent diabetes mellitus (IDDM) because of its inhibition of insulin secretion, direct cytotoxicity, and alteration of islet cell antigen expression.
51	8746789	Because transforming growth factor beta (TGF-beta) has been reported to inhibit IL-1 receptor expression in several lymphoid and progenitor cell lines, to induce IL-1 receptor antagonist protein (IRAP) production in human peripheral blood monocytes, and to antagonize several effects of inflammatory cytokines and because oral tolerance may be mediated in part by TGF-beta released by regulatory T lymphocytes, we investigated whether TGF-beta counteracted the effects of IL-1 beta on islet cells.
52	8746789	Islets isolated from Sprague-Dawley rats were cultured with or without recombinant human IL-1 beta and TGF-beta.
53	8746789	Accumulated insulin secretion, cytokine-induced cytotoxicity, and islet cell expression of glutamic acid decarboxylase 65 (GAD-65) and heat-shock protein 70 (HSP-70) were measured in this study.
54	8746789	We found that (1) IL-1 beta at 50 and 100 pg/ml inhibited insulin secretion by 41.9 +/- 14.8 and 52.6 +/- 3.5% and induced cytotoxicity by 46.5 +/- 17.3 and 54.1 +/- 6.1%, respectively.
55	8746789	IL-1 beta at 1000 pg/ml significantly increased HSP-70 expression and decreased GAD-65 expression. (2) TGF-beta at 0.1, 1, 10, and 40 ng/ml had no significant effect on insulin secretion and did not induce cytotoxicity, TGF-beta at 40 ng/ml had no effect on the expression of either HSP-70 or GAD-65. (3) In combination, TGF-beta at 1, 10, and 40 ng/ml did not antagonize the IL-1 beta (50 and 100 pg/ml)-induced inhibition of insulin secretion or cytotoxicity; TGF-beta (40 ng/ml) did not block the effects of IL-1 beta (1000 pg/ml) on HSP-70 or GAD-65 expression.
56	8746789	In conclusion, recombinant human TGF-beta does not counteract these effects of recombinant human IL-1 beta on rat pancreatic islet cells.
57	8779862	Roles of IL-1 and TNF-alpha in endotoxin-induced activation of nitric oxide synthase in cultured rat brain cells.
58	8779862	In astrocytes and microglia, bacterial lipopolysaccharide (LPS) stimulates production and release of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO).
59	8779862	Although IL-1 beta and TNF-alpha are themselves capable of inducing NO synthase (NOS) in glia, the specific factors mediating LPS induction of NOS in brain have not been identified.
60	8779862	To determine whether LPS induction of NOS in brain cells is mediated by IL-1 or TNF-alpha, acting alone or in concert, the effects of IL-1-receptor antagonist (IL-1Ra) and of TNF-soluble receptor (TNFsRp55), presented individually and in combination, on LPS-induced NOS activity were tested.
61	8779862	In glial-enriched mixed primary cultures of neonatal rat telencephalic cells, LPS (0.1-100 ng/ml), IL-1 beta (0.01-10 nM), and TNF-alpha (0.1-100 nM) each concentration dependently stimulated accumulation of nitrite, an indicator of NO production.
62	8779862	Induction of nitrite accumulation by LPS and by IL-1 was blocked by N omega-nitro-L-arginine methyl ester and N omega-monomethyl-L-arginine, indicating that it was mediated by NOS.
63	8779862	TNF-alpha alone induced NO production weakly as compared with IL-1, but combined submaximal concentrations of IL-1 beta (1 nM) and TNF-alpha (10 nM) induced NOS synergistically.
64	8779862	The results indicate that LPS induction of NOS activity in brain cells is mediated in part by both IL-1 beta and TNF-alpha.
65	8786086	Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus.
66	8786086	We have previously found association between an allele of the interleukin-1 (IL-1) receptor antagonist gene (IL1RN) and several inflammatory diseases, where IL-1 has been implicated in the inflammatory mechanism.
67	8788310	Effect of interleukin-1a, IL-1b and IL-1 receptor antibody on the proliferation and steroidogenesis of regenerating rat adrenal cortex.
68	8788310	The animals were given purified human recombinant IL-1 alpha (5 micrograms/kg), IL-1 beta (5 micrograms/kg) anti-human IL-1 receptor antibody (10 micrograms/kg) and combination of interleukins and antibodies.
69	8788310	Effect of interleukin-1a, IL-1b and IL-1 receptor antibody on the proliferation and steroidogenesis of regenerating rat adrenal cortex.
70	8788310	The animals were given purified human recombinant IL-1 alpha (5 micrograms/kg), IL-1 beta (5 micrograms/kg) anti-human IL-1 receptor antibody (10 micrograms/kg) and combination of interleukins and antibodies.
71	9112337	Interleukin 1 beta, tumour necrosis factor-alpha and interleukin 1 receptor antagonist in newly diagnosed insulin-dependent diabetes mellitus: comparison to long-standing diabetes and healthy individuals.
72	9112337	Interleukin 1 beta (IL-1) and tumour necrosis factor alpha (TNF) are important for the beta cell lysis in insulin-dependent diabetes mellitus (IDDM), while IL-1 receptor antagonist (IL-1ra) is considered protective by blocking the effects of IL-1.
73	9112337	Serum concentrations and ex-vivo production of IL-1, TNF and IL-1ra were examined in 10 newly diagnosed IDDM (ND-IDDM) patients, and compared with 11 long-standing IDDM (LS-IDDM) patients and 14 healthy volunteers.
74	9112337	Ex-vivo LPS-stimulated production of IL-1 in ND-IDDM patients was significantly increased compared with LS-IDDM patients and healthy controls, while TNF and IL-1ra synthesis did not differ significantly.
75	9112337	IL-1ra/IL-1 ratio was significantly decreased in ND-IDDM, and returned to normal values in the LS-IDDM group.
76	9158104	IL-1 receptor antagonist inhibits recurrence of disease after syngeneic pancreatic islet transplantation to spontaneously diabetic non-obese diabetic (NOD) mice.
77	9158104	The effect of an IL-1 receptor antagonist on recurrence of hyperglycaemia after syngeneic pancreatic islet transplantation to spontaneously diabetic female NOD mice was investigated.
78	9158104	Administration of IL-1 receptor antagonist had a clear protective effect against recurrence of hyperglycaemia until day 14, but after cessation of drug delivery hyperglycaemia re-appeared.
79	9158104	The results indicate that continuous administration of the IL-1 receptor antagonist can prevent recurrence of the diabetogenic process in NOD mice.
80	9158104	IL-1 receptor antagonist may therefore become a useful adjuvant immunomodulating therapy after human islet transplantation in insulin-dependent diabetes mellitus.
81	9158104	IL-1 receptor antagonist inhibits recurrence of disease after syngeneic pancreatic islet transplantation to spontaneously diabetic non-obese diabetic (NOD) mice.
82	9158104	The effect of an IL-1 receptor antagonist on recurrence of hyperglycaemia after syngeneic pancreatic islet transplantation to spontaneously diabetic female NOD mice was investigated.
83	9158104	Administration of IL-1 receptor antagonist had a clear protective effect against recurrence of hyperglycaemia until day 14, but after cessation of drug delivery hyperglycaemia re-appeared.
84	9158104	The results indicate that continuous administration of the IL-1 receptor antagonist can prevent recurrence of the diabetogenic process in NOD mice.
85	9158104	IL-1 receptor antagonist may therefore become a useful adjuvant immunomodulating therapy after human islet transplantation in insulin-dependent diabetes mellitus.
86	9158104	IL-1 receptor antagonist inhibits recurrence of disease after syngeneic pancreatic islet transplantation to spontaneously diabetic non-obese diabetic (NOD) mice.
87	9158104	The effect of an IL-1 receptor antagonist on recurrence of hyperglycaemia after syngeneic pancreatic islet transplantation to spontaneously diabetic female NOD mice was investigated.
88	9158104	Administration of IL-1 receptor antagonist had a clear protective effect against recurrence of hyperglycaemia until day 14, but after cessation of drug delivery hyperglycaemia re-appeared.
89	9158104	The results indicate that continuous administration of the IL-1 receptor antagonist can prevent recurrence of the diabetogenic process in NOD mice.
90	9158104	IL-1 receptor antagonist may therefore become a useful adjuvant immunomodulating therapy after human islet transplantation in insulin-dependent diabetes mellitus.
91	9158104	IL-1 receptor antagonist inhibits recurrence of disease after syngeneic pancreatic islet transplantation to spontaneously diabetic non-obese diabetic (NOD) mice.
92	9158104	The effect of an IL-1 receptor antagonist on recurrence of hyperglycaemia after syngeneic pancreatic islet transplantation to spontaneously diabetic female NOD mice was investigated.
93	9158104	Administration of IL-1 receptor antagonist had a clear protective effect against recurrence of hyperglycaemia until day 14, but after cessation of drug delivery hyperglycaemia re-appeared.
94	9158104	The results indicate that continuous administration of the IL-1 receptor antagonist can prevent recurrence of the diabetogenic process in NOD mice.
95	9158104	IL-1 receptor antagonist may therefore become a useful adjuvant immunomodulating therapy after human islet transplantation in insulin-dependent diabetes mellitus.
96	9158104	IL-1 receptor antagonist inhibits recurrence of disease after syngeneic pancreatic islet transplantation to spontaneously diabetic non-obese diabetic (NOD) mice.
97	9158104	The effect of an IL-1 receptor antagonist on recurrence of hyperglycaemia after syngeneic pancreatic islet transplantation to spontaneously diabetic female NOD mice was investigated.
98	9158104	Administration of IL-1 receptor antagonist had a clear protective effect against recurrence of hyperglycaemia until day 14, but after cessation of drug delivery hyperglycaemia re-appeared.
99	9158104	The results indicate that continuous administration of the IL-1 receptor antagonist can prevent recurrence of the diabetogenic process in NOD mice.
100	9158104	IL-1 receptor antagonist may therefore become a useful adjuvant immunomodulating therapy after human islet transplantation in insulin-dependent diabetes mellitus.
101	9375806	The cytokine interleukin-1beta (IL-1beta) has been shown to inhibit insulin secretion and destroy pancreatic islets by a mechanism that involves the expression of inducible nitric oxide synthase (iNOS), and the production of nitric oxide (NO).
102	9375806	Insulin containing beta-cells, selectively destroyed during the development of autoimmune diabetes, appear to be the islet cellular source of iNOS following treatment with IL-1beta.
103	9375806	We show that the interleukin-1 receptor antagonist protein (IRAP) prevents IL-1beta-induced nitrite formation and IL-1beta-induced inhibition of insulin secretion by isolated islets and primary beta-cells purified by fluorescence-activated cell sorting (FACS).
104	9375806	The protective effects of IRAP correlate with an inhibition of IL-1beta-induced iNOS expression by islets and FACS purified beta-cells.
105	9375806	To provide direct evidence to support beta-cell expression of IL-1 type I signaling receptors, we show that antiserum specific for the type I IL-1 receptor neutralizes IL-1beta-induced nitrite formation by RINm5F cells, and that RINm5F cells express the type I IL-1 receptor at the protein level.
106	9691088	The purpose of this study was to determine if the endogenous production and release of interleukin 1 (IL-1) in human islets of Langerhans by resident macrophages results in the inhibition of beta cell function.
107	9691088	Treatment of human islets with a combination of tumor necrosis factor (TNF) + lipopolysaccharide (LPS) + interferon-gamma (IFN-gamma) stimulates inducible nitric oxide synthase (iNOS) expression, nitric oxide production, and inhibits glucose-stimulated insulin secretion.
108	9691088	The IL-1 receptor antagonist protein (IRAP) prevents TNF + LPS + IFN-gamma-induced iNOS expression and nitrite production, and attenuates the inhibitory effects on glucose-stimulated insulin secretion by human islets.
109	9691088	Inhibition of iNOS activity by aminoguanidine also attenuates TNF + LPS + IFN-gamma-induced inhibition of insulin secretion by human islets.
110	9691088	These results indicate that the inhibitory effects of TNF + LPS + IFN-gamma are mediated by nitric oxide, produced by the actions of IL-1 released endogenously within human islets.
111	9691088	Reverse transcriptase polymerase chain reaction was used to confirm that TNF + LPS + IFN-gamma stimulates the expression of both IL-1alpha and IL-1beta in human islets.
112	9691088	Two forms of evidence indicate that resident macrophages are the human islet cellular source of IL-1: culture conditions that deplete islet lymphoid cells prevent TNF + LPS + IFN-gamma-induced iNOS expression, nitric oxide production, and IL-1 mRNA expression by human islets; and IL-1 and the macrophage surface marker CD69 colocalize in human islets treated with TNF + LPS + IFN-gamma as determined by immunohistochemical analysis.
113	9691088	Lastly, nitric oxide production is not required for TNF + LPS + IFN-gamma-induced IL-1 release in human islets.
114	9691088	These findings support the hypothesis that activated islet macrophages may mediate beta cell damage during the development of insulin-dependent diabetes by releasing IL-1 in human islets followed by cytokine-induced iNOS expression by beta cells.
115	9923604	Interleukin-1beta activates a short STAT-3 isoform in clonal insulin-secreting cells.
116	9923604	In the present work we describe induction of DNA binding activity to signal transducer and activator of transcription (STAT) in response to IL-1beta in clonal insulin-secreting cells.
117	9923604	Moreover, IL-1beta activates a short isoform of STAT-3 that potently stimulates transcription.
118	9923604	Immunoprecipitation studies reveal an interaction between the activated STAT-3 and the IL-1 receptor accessory protein indicating an association between the two signaling pathways.
119	10480601	Adenoviral gene transfer of the interleukin-1 receptor antagonist protein to human islets prevents IL-1beta-induced beta-cell impairment and activation of islet cell apoptosis in vitro.
120	10480601	In particular, IL-1beta can impair glucose-stimulated insulin production in beta-cells in vitro and can sensitize them to Fas (CD95)/FasL-triggered apoptosis.
121	10480601	In this report, we have examined the ability to block the detrimental effects of IL-1beta by genetically modifying islets by adenoviral gene transfer to express the IL-1 receptor antagonist protein.
122	10480601	We demonstrate that adenoviral gene delivery of the cDNA encoding the interleukin-1 receptor antagonist protein (IL-1Ra) to cultured islets results in protection of human islets in vitro against IL-1beta-induced nitric oxide formation, impairment in glucose-stimulated insulin production, and Fas-triggered apoptosis activation.
123	10671304	Linkage disequilibrium testing of four interleukin-1 gene-cluster polymorphisms in Danish multiplex families with insulin-dependent diabetes mellitus.
124	10671304	The molecules of the interleukin 1 (IL-1) system have been suggested to play a role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM), and polymorphisms in the genes encoding IL-1beta (IL1B), the IL-1 Type 1 receptor (IL1RTI) and the IL-1 receptor antagonist (IL1RN) molecules have been associated with IDDM in case-control studies.
125	10671304	Hence, by means of the TDT we have investigated four intragenic IL-1 gene-cluster polymorphisms, the IL1B AvaI, the IL1B TaqI, the IL1RTI PstI and the IL1RN 2(nd)intron polymorphisms, for linkage and intra-familial association with IDDM in Danish IDDM multiplex family material comprising 245 families.
126	10671304	In conclusion, by means of intra-familial TDT analysis we found no linkage or intra-familial association between IDDM and the four IL-1 gene-cluster polymorphisms in Danish IDDM multiplex family material.
127	10826510	The interleukin-1 (IL-1) family of molecules is together with other cytokines an integral component of the complex intercellular communication required to mount and control an immune response.
128	10826510	IL-1 stimulates the guanylate mediated pathways and inhibits the adenylate cyclase mediated pathways.
129	10826510	All IL-1 effects are counteracted by IL-1 receptor antagonist indicating that the effects are exerted through activation of specific IL-1 receptors on thyrocytes.
130	10871193	To this end, we have cultured INS-1 insulinoma cells in increasing concentrations of interleukin-1beta (IL-1beta) + gamma-interferon (IFN-gamma), with approximate weekly iterations over an 8-week period.
131	10871193	These cells were also 78 +/- 1.2% viable after 5 days of exposure to the combination of 10 ng/ml IL-1beta and 100 U/ml IFN-gamma, whereas parental INS-1 cells treated in the same manner were only 0.3 +/- 0.03% viable.
132	10871193	The resistance to IL-1beta conferred by this procedure was stable, whereas the partial resistance to IFN-gamma was transient but reinducible by culture in the presence of cytokines.
133	10871193	Stable transfection of INS-1res cells with a plasmid containing the human insulin cDNA and expansion of the transfected colonies in the absence of cytokines produced cell lines that were on average more resistant to IL-1beta + IFN-gamma (53 +/- 11%) than similarly transfected clones derived from parental INS-1 cells (15 +/- 7%).
134	10871193	With regard to the mechanism by which selection was conferred, we found normal levels of IFN-gamma receptor mRNA, but a 60% reduction in expression of the IL-1 receptor type I (IL-1RI) in INS-1res cells compared with parental INS-1 cells.
135	10871193	IL-1beta signaling through p38 MAP kinase was found to be normal in INS-1res cells, suggesting that their expression of IL-1RI is sufficient to maintain cytokine action.
136	10871193	However, normal IL-1beta-mediated translocation of NF-kappaB and induction of inducible nitric oxide synthase expression and nitric oxide production was severely impaired in the INS-1res cell lines, suggesting a mechanism for the IL-1beta resistance.
137	10953913	Genes encoding transforming growth factor beta, interleukin-4 (IL-4) and IL-10 are most frequently protective.
138	10953913	Autoimmune/ inflammatory diseases are associated with excessive production of inflammatory cytokines such as IL-1, IL-12, tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma).
139	10953913	Vectors encoding inhibitors of these cytokines, such as IL-1 receptor antagonist, soluble IL-1 receptors, IL-12p40, soluble TNFalpha receptors or IFNgamma-receptor/IgG-Fc fusion proteins are protective in models of either arthritis, Type 1 DM, SLE or EAE.
140	10967106	Dominant negative MyD88 proteins inhibit interleukin-1beta /interferon-gamma -mediated induction of nuclear factor kappa B-dependent nitrite production and apoptosis in beta cells.
141	10967106	In the present study, we investigated whether the interleukin (IL)-1beta intracellular signal transduction pathway could be blocked by overexpression of dominant negative forms of the IL-1 receptor interacting protein MyD88.
142	10967106	We show that overexpression of the Toll domain or the lpr mutant of MyD88 in betaTc-Tet cells decreased nuclear factor kappaB (NF-kappaB) activation upon IL-1beta and IL-1beta/interferon (IFN)-gamma stimulation.
143	10967106	Inducible nitric oxide synthase mRNA accumulation and nitrite production, which required the simultaneous presence of IL-1beta and IFN-gamma, were also suppressed by approximately 70%, and these cells were more resistant to cytokine-induced apoptosis as compared with parental cells.
144	10967106	The decrease in glucose-stimulated insulin secretion induced by IL-1beta and IFN-gamma was however not prevented.
145	10967106	This was because these dysfunctions were induced by IFN-gamma alone, which decreased cellular insulin content and stimulated insulin exocytosis.
146	10967106	These results demonstrate that IL-1beta is involved in inducible nitric oxide synthase gene expression and induction of apoptosis in mouse beta cells but does not contribute to impaired glucose-stimulated insulin secretion.
147	10967106	Furthermore, our data show that IL-1beta cellular actions can be blocked by expression of MyD88 dominant negative proteins and, finally, that cytokine-induced beta cell secretory dysfunctions are due to the action of IFN-gamma.
148	11727511	Administration of cDNA encoding soluble IFN-gamma receptor (IFN-gamma R)/IgG-Fc fusion proteins, soluble TNF-alpha receptors, or IL-1 receptor antagonist (IL-1ra), protects against either lupus, various forms of arthritis, autoimmune diabetes, or other autoimmune diseases.
149	11889184	IL-1 receptor antagonist serum levels are increased in human obesity: a possible link to the resistance to leptin?
150	11889184	We have recently shown that human monocytic cells express functional leptin receptors and that leptin is capable of inducing the expression and secretion of the IL-1 receptor antagonist (IL-1Ra).
151	11889184	Serum IL-1Ra concentrations proved to be elevated 6.5-fold in the obese subjects, and they were positively correlated in a linear manner with the leptin levels (r(2) = 0.34; P = 0.01), although lean body mass (LBM) and the insulin resistance index were even better predictors of IL-1Ra levels (r(2) = 0.45 and 0.58, respectively; P < 0.01).
152	11889184	However, LBM and insulin resistance are better predictors of serum IL-1Ra concentrations than are leptin levels, suggesting that additional metabolic factors control the secretion of this cytokine antagonist.
153	11889184	IL-1 receptor antagonist serum levels are increased in human obesity: a possible link to the resistance to leptin?
154	11889184	We have recently shown that human monocytic cells express functional leptin receptors and that leptin is capable of inducing the expression and secretion of the IL-1 receptor antagonist (IL-1Ra).
155	11889184	Serum IL-1Ra concentrations proved to be elevated 6.5-fold in the obese subjects, and they were positively correlated in a linear manner with the leptin levels (r(2) = 0.34; P = 0.01), although lean body mass (LBM) and the insulin resistance index were even better predictors of IL-1Ra levels (r(2) = 0.45 and 0.58, respectively; P < 0.01).
156	11889184	However, LBM and insulin resistance are better predictors of serum IL-1Ra concentrations than are leptin levels, suggesting that additional metabolic factors control the secretion of this cytokine antagonist.
157	12160520	Regulation of the interleukin-1 receptor antagonist in THP-1 cells by ligands of the peroxisome proliferator-activated receptor gamma.
158	12160520	High concentrations of PPARgamma ligands were shown to have anti-inflammatory activities by inhibiting the secretion of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFalpha) by stimulated monocytes.
159	12160520	The aim of this study was to determine whether PGJ2 and TZDs would also exert an immunomodulatory action through the up-regulation of anti-inflammatory cytokines such as the IL-1 receptor antagonist (IL-1Ra).
160	12160520	THP-1 monocytic cells were stimulated with PMA, thereby enhancing the secretion of IL-1, IL-6, TNFalpha, IL-1Ra and metalloproteinases.
161	12160520	Addition of PGJ2 had an inhibitory effect on IL-1, IL-6 and TNFalpha secretion, while increasing IL-1Ra production.
162	12160520	In contrast, the bona fide PPARgamma ligands (TZDs; rosiglitazone, pioglitazone and troglitazone) barely inhibited proinflammatory cytokines, but strongly enhanced the production of IL-1Ra from PMA-stimulated THP-1 cells.
163	12160520	Unstimulated cells did not respond to TZDs in terms of IL-1Ra production, suggesting that in order to be effective, PPAR ligands depend on PMA signalling.
164	12235117	IL-1beta inhibits beta cell function and promotes Fas-triggered apoptosis in part by activating the transcription factor NF-kappaB.
165	12235117	In vitro exposure of islets from nondiabetic organ donors to high glucose levels resulted in increased production and release of IL-1beta, followed by NF-kappaB activation, Fas upregulation, DNA fragmentation, and impaired beta cell function.
166	12235117	The IL-1 receptor antagonist protected cultured human islets from these deleterious effects. beta cells themselves were identified as the islet cellular source of glucose-induced IL-1beta.
167	12235117	These findings implicate an inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes and identify the IL-1beta/NF-kappaB pathway as a target to preserve beta cell mass and function in this condition.
168	12242022	Monocytes are one of the target cells of leptin, and we have demonstrated that secretion of L-1Ra, an IL-1 receptor antagonist, is induced by leptin.
169	12861041	The therapeutic benefit of the anti-DNP fraction was associated with the inhibition of secretion of proinflammatory cytokines and stimulation of secretion of IL-1 receptor antagonist.
170	14556867	C-reactive protein (CRP, microg/ml), interleukin (IL)-6 (pg/ml), IL-1 receptor antagonist (pg/ml), and soluble CD40 ligand (ng/ml) were assayed in each sample by enzyme-linked immunosorbent assay.
171	14556867	Preprocedural concentrations of IL-6, IL-1 receptor antagonist, and soluble CD40 ligand tended to be greater in patients with diabetes.
172	14556867	C-reactive protein (CRP, microg/ml), interleukin (IL)-6 (pg/ml), IL-1 receptor antagonist (pg/ml), and soluble CD40 ligand (ng/ml) were assayed in each sample by enzyme-linked immunosorbent assay.
173	14556867	Preprocedural concentrations of IL-6, IL-1 receptor antagonist, and soluble CD40 ligand tended to be greater in patients with diabetes.
174	14693705	IL-1 receptor deficiency slows progression to diabetes in the NOD mouse.
175	14693705	They act by upregulation of genes including Fas and inducible nitric oxide synthase (iNOS), which have both been shown to lead to beta-cell death in vitro.
176	14693705	We used mice deficient in the interleukin (IL)-1 receptor (IL-1R) to assess the contribution of IL-1 to different models of diabetes.
177	14693705	IL-1R-deficient islets were protected from the damaging effects of tumor necrosis factor (TNF) and interferon (IFN)-gamma in vitro, and beta-cell expression of iNOS was reduced, suggesting that IL-1 mediates the induction of iNOS by TNF and IFN-gamma.
178	14693705	IL-1 action was not required for induction of class I major histocompatibility complex or Fas by TNF and IFN-gamma.
179	14693705	IL-1 receptor deficiency slows progression to diabetes in the NOD mouse.
180	14693705	They act by upregulation of genes including Fas and inducible nitric oxide synthase (iNOS), which have both been shown to lead to beta-cell death in vitro.
181	14693705	We used mice deficient in the interleukin (IL)-1 receptor (IL-1R) to assess the contribution of IL-1 to different models of diabetes.
182	14693705	IL-1R-deficient islets were protected from the damaging effects of tumor necrosis factor (TNF) and interferon (IFN)-gamma in vitro, and beta-cell expression of iNOS was reduced, suggesting that IL-1 mediates the induction of iNOS by TNF and IFN-gamma.
183	14693705	IL-1 action was not required for induction of class I major histocompatibility complex or Fas by TNF and IFN-gamma.
184	15141093	Leptin modulates beta cell expression of IL-1 receptor antagonist and release of IL-1beta in human islets.
185	15141093	IL-1 receptor antagonist (IL-1Ra) is a naturally occurring antagonist of IL-1beta and protects cultured human islets from glucotoxicity.
186	15141093	Therefore, the balance of IL-1beta and IL-1Ra may play a crucial role in the pathogenesis of diabetes.
187	15141093	In vitro, chronic exposure of human islets to leptin, a hormone secreted by adipocytes, decreased beta cell production of IL-1Ra and induced IL-1beta release from the islet preparation, leading to impaired beta cell function, caspase-3 activation, and apoptosis.
188	15141093	These findings demonstrate expression of IL-1Ra in the human beta cell, providing localized protection against leptin- and glucose-induced islet IL-1beta.
189	15141093	Leptin modulates beta cell expression of IL-1 receptor antagonist and release of IL-1beta in human islets.
190	15141093	IL-1 receptor antagonist (IL-1Ra) is a naturally occurring antagonist of IL-1beta and protects cultured human islets from glucotoxicity.
191	15141093	Therefore, the balance of IL-1beta and IL-1Ra may play a crucial role in the pathogenesis of diabetes.
192	15141093	In vitro, chronic exposure of human islets to leptin, a hormone secreted by adipocytes, decreased beta cell production of IL-1Ra and induced IL-1beta release from the islet preparation, leading to impaired beta cell function, caspase-3 activation, and apoptosis.
193	15141093	These findings demonstrate expression of IL-1Ra in the human beta cell, providing localized protection against leptin- and glucose-induced islet IL-1beta.
194	15379752	C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease.
195	15379752	Production of CRP is regulated by interleukin (IL)-1beta, IL-1 receptor antagonist and IL-6.
196	15379752	In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL-1B(-511), IL-1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL-1RN [IL-1RN(VNTR)], IL-6(-174) and IL-6(-572).
197	15379752	In univariate analysis, carrier status for the IL-1B(+3954)T allele and IL-1RN(VNTR) allele 2 [IL-1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log-CRP values, respectively.
198	15379752	After adjustment for non-genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL-1B(+3954)T than in non-carriers: mean log-CRP (with 95% confidence interval) was 0.443 (0.311-0.574) for CT or TT genotypes compared with 0.240 (0.107-0.373) for the CC genotype, which corresponded to back-transformed CRP levels of 2.77 and 1.74 mg l(-1), respectively.
199	15379752	Adjusted association was also significant for IL-1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log-CRP value was 0.252 (0.115-0.388) for carriers and 0.421 (0.290-0.552) for non-carriers (CRP 1.79 and 2.64 mg l(-1), respectively).
200	15379752	When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL-1B(+3954)T (P < 0.05), but not for IL-1RN(VNTR)*2.
201	15379752	We conclude that IL-1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors.
202	15379752	Our data also suggest a possible relationship of IL-1RN(VNTR)*2 with lower CRP levels in the same patients.
203	15512788	These genes, indoleamine 2,3-dioxygenase (IDO), manganese superoxide dismutase (MnSOD), and interleukin (IL)-1 receptor antagonist protein (IRAP), were transferred to isolated NOD donor islets ex vivo then transplanted to NODscid recipients and evaluated in vivo after diabetogenic T-cell challenge.
204	15539803	In previous studies we have shown that elevated glucose concentrations induce apoptosis in human beta-cells due to an interaction between constitutively expressed Fas ligand and upregulated Fas.
205	15539803	This was antagonized by the IL-1 receptor antagonist (IL-1Ra), a naturally occurring anti-inflammatory cytokine also found in the beta-cell.
206	15539803	Therefore the balance of IL-1beta and IL-1Ra may play a crucial role in the pathogenesis of diabetes.
207	15578044	Adenoviral overexpression of interleukin-1 receptor antagonist protein increases beta-cell replication in rat pancreatic islets.
208	15578044	The naturally occurring inhibitor of interleukin-1 (IL-1) action, interleukin-1 receptor antagonist protein (IRAP), binds to the type 1 IL-1 receptor but does not initiate IL-1 signal transduction.
209	15578044	In this study, we have determined the effects of IL-1beta and IRAP overexpression on adult beta-cell replication and viability.
210	15578044	This effect was completely prevented in islets overexpressing IRAP after adenoviral gene transfer at 5.5 mM (Ad-IL-1Ra+IL-1beta: 0.84+/-0.1%, P<0.05) and 22.2 mM glucose (Ad-IL-1Ra+IL-1beta: 1.22+/-0.2%, P<0.05).
211	15578044	Moreover, overexpression of IRAP increased glucose-stimulated beta-cell replication in the absence of IL-1beta exposure (Ad-IL-1Ra: 1.59+/-0.5%, P<0.05). beta-Cell death (TUNEL technique) was increased in IL-1beta-exposed islets but not in Ad-IL-1Ra-infected islets (control: 0.82+/-0.2%; control+IL-1beta: 1.77+/-0.2; IRAP: 0.61+/-0.2%; IRAP+IL-1beta: 0.86+/-0.1%, P<0.05).
212	15578044	This study shows that in addition to the effects of IL-1beta on beta-cell viability, this cytokine exerts a deleterious action on beta-cell replication, which can be prevented by IRAP overexpression, and provides support for the potential use of IRAP as a therapeutic tool.
213	15772055	Adipose tissue contributes to the production of TNF-alpha, which is reflected by elevated levels of soluble TNF-alpha receptors, IL-6, IL-1 receptor antagonist, and C-reactive protein.
214	15772055	We suggest that TNF-alpha rather than IL-6 is the driver behind insulin resistance and dyslipidemia and that IL-6 is a marker of the metabolic syndrome, rather than a cause.
215	15772055	During exercise, IL-6 is produced by muscle fibers via a TNF-independent pathway.
216	15772055	IL-6 stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra and IL-10 and inhibits the production of the proinflammatory cytokine TNF-alpha.
217	15772055	We suggest that regular exercise induces suppression of TNF-alpha and thereby offers protection against TNF-alpha-induced insulin resistance.
218	15814729	Importantly, IL-1R antagonist and type 2 IL-1 receptor (IL-1R2) failed to up-regulate in response to LPS in db/db mice.
219	15849359	Phosphorylation of Ser24 in the pleckstrin homology domain of insulin receptor substrate-1 by Mouse Pelle-like kinase/interleukin-1 receptor-associated kinase: cross-talk between inflammatory signaling and insulin signaling that may contribute to insulin resistance.
220	15849359	Mouse Pelle-like kinase (mPLK, homolog of human IL-1 receptor-associated kinase (IRAK)) participates in inflammatory signaling.
221	15849359	We evaluated IRS-1 as a novel substrate for mPLK that may contribute to linking inflammation with insulin resistance.
222	15849359	Wild-type mPLK, but not a kinase-inactive mutant (mPLK-KD), directly phosphorylated full-length IRS-1 in vitro.
223	15849359	This in vitro phosphorylation was increased when mPLK was immunoprecipitated from tumor necrosis factor (TNF)-alpha-treated cells.
224	15849359	In NIH-3T3(IR) cells, wild-type mPLK (but not mPLK-KD) co-immunoprecipitated with IRS-1.
225	15849359	Using mass spectrometry, we identified Ser(24) in the pleckstrin homology (PH) domain of IRS-1 as a specific phosphorylation site for mPLK.
226	15849359	IRS-1 mutants S24D or S24E (mimicking phosphorylation at Ser(24)) had impaired ability to associate with insulin receptors resulting in diminished tyrosine phosphorylation of IRS-1 and impaired ability of IRS-1 to bind and activate PI-3 kinase in response to insulin.
227	15849359	IRS-1-S24D also had an impaired ability to mediate insulin-stimulated translocation of GLUT4 in rat adipose cells.
228	15849359	Importantly, endogenous mPLK/IRAK was activated in response to TNF-alpha or interleukin 1 treatment of primary adipose cells.
229	15849359	In addition, using a phospho-specific antibody against IRS-1 phosphorylated at Ser(24), we found that interleukin-1 or TNF-alpha treatment of Fao cells stimulated increased phosphorylation of endogenous IRS-1 at Ser(24).
230	15849359	We conclude that IRS-1 is a novel physiological substrate for mPLK.
231	15849359	TNF-alpha-regulated phosphorylation at Ser(24) in the pleckstrin homology domain of IRS-1 by mPLK/IRAK represents an additional mechanism for cross-talk between inflammatory signaling and insulin signaling that may contribute to metabolic insulin resistance.
232	15917841	Gene expression and/or medium concentrations of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1 RA), TNFalpha, IL-6, IL-8, resistin, PAI-1 and leptin were analysed.
233	15917841	TNFalpha increased the mRNA levels of TNFalpha itself as well as IL-6, IL-8, IL-1beta and PAI-1, but not leptin.
234	15917841	The medium concentrations of IL-1 RA, IL-6 and IL-8 were markedly increased by TNFalpha while no measurable release of TNFalpha, resistin or IL-1beta to the medium was found.
235	15917841	Thus, human adipose tissue from nonobese individuals releases substantial amounts of IL-6, IL-8 and IL-1 RA and the gene expression of these cytokines, like that of IL-1beta and PAI-1, is regulated by TNFalpha.
236	15917841	However, since neither TNFalpha, resistin or IL-1beta was found in the culture medium, such a regulatory effect by TNFalpha on adipose tissue in vivo is likely to be mediated through a paracrine mechanism where invaded inflammatory cells may play a critical role.
237	16174285	Among them, -511 C/T in interleukin-1beta (IL-1beta), tandem repeat in IL-1 receptor antagonist (IL-1Ra), -308 G/A in tumour necrosis factor-alpha (TNF-alpha) were significantly associated with an increased risk of kidney failure.
238	16249450	It has been recently suggested that high glucose-induced beta-cell apoptosis in type 2 diabetes shares a final common pathway with type 1 diabetes, involving interleukin-1beta (IL-1beta) production by beta-cells, nuclear factor-kappaB (NF-kappaB) activation, and death via Fas-FasL.
239	16249450	The aim of this study was to test whether human islet exposure to high glucose in vitro, or to the type 2 diabetes environment in vivo, induces IL-1beta expression and consequent activation of NF-kappaB-dependent genes.
240	16249450	Culture of the human islets at 11 and 28 mmol/l glucose induced a four- to fivefold increase in medium insulin as compared with 5.6 mmol/l glucose, but neither IL-1beta nor IL-1 receptor antagonist (IL-1ra) expression changed.
241	16249450	IL-1beta and IL-1ra protein release to the medium was also unchanged.
242	16249450	Expression of the NF-kappaB-dependent genes IkappaB-alpha and monocyte chemoattractant protein (MCP)-1 was induced in human islets by IL-1beta but not by high glucose.
243	16249450	The findings on mRNA levels were essentially the same as in the in vitro experiments, namely the in vivo diabetic state did not induce IL-1beta, Fas, or MCP-1 expression in human islets, and also did not modify IL-1ra expression.
244	16249450	The present findings suggest that high glucose in vitro, or the diabetic milieu in vivo, does not induce IL-1beta production or NF-kappaB activation in human islets.
245	16306368	Decreased fat mass in interleukin-1 receptor antagonist-deficient mice: impact on adipogenesis, food intake, and energy expenditure.
246	16306368	Because the soluble IL-1 receptor antagonist (IL-1Ra) is markedly increased in the serum of obese patients and is overexpressed in white adipose tissue in obesity, we studied the metabolic consequences of genetic IL-1Ra ablation in mice.
247	16306368	Interestingly, IL-1Ra-/- and IL-1Ra+/- mice presented an attenuation in high-fat diet-induced caloric hyperphagia, indicating a better adaptation to hypercaloric alimentation, which is in line with the role of IL-1Ra as a mediator of leptin resistance.
248	16567518	Combined interleukin-6 and interleukin-1 deficiency causes obesity in young mice.
249	16567518	Proinflammatory cytokines including interleukin (IL)-1 and IL-6 exert pleiotropic effects on the neuro-immuno-endocrine system.
250	16567518	Previously, we showed that IL-1 receptor antagonist-deficient (IL-1Ra(-/-)) mice show a lean phenotype due to an abnormal lipid metabolism.
251	16567518	This study sought to assess the roles of IL-1 and IL-6 in body weight homeostasis.
252	16567518	We generated mice deficient in IL-6 and IL-1Ra (IL-6(-/-) IL-1Ra(-/-)) and IL-6, IL-1alpha, and IL-1beta (IL-6(-/-) IL-1(-/-)).
253	16567518	IL-6(-/-) IL-1Ra(-/-) mice exhibited a lean phenotype, similar to IL-1Ra(-/-) mice.
254	16567518	On the other hand, IL-6(-/-) IL-1(-/-) mice became obese as early as 10 weeks of age, while IL-1(-/-) mice and IL-6(-/-) mice were normal at this age.
255	16567518	The daily food intake was significantly higher in IL-6(-/-) IL-1(-/-) mice than in IL-6(-/-) IL-1(+/-) mice, while energy expenditure was comparable in these two strains.
256	16567518	Acute anorexia induced by peripheral administration of IL-1 was significantly suppressed in IL-6(-/-) IL-1(-/-) mice, but not in IL-1(-/-) mice or IL-6(-/-) mice compared with wild-type mice.
257	16567518	These results indicate that IL-1 and IL-6 are both involved in the regulation of body fat in a redundant manner in young mice.
258	16644698	The IL-1 cytokine trap used herein comprised extracellular domains of the IL-1 receptor accessory protein and the human IL-1 receptor 1 arranged inline and fused to the Fc portion of human IgG1.
259	16644698	IL-1beta alone induced a strong inhibition of insulin secretion and glucose oxidation rate and a marked increase in medium nitrite accumulation as an indicator of nitric oxide generation.
260	16644698	Moreover, the IL-1 trap (100:1) blocked the increased islet cell death seen in islets treated with a combination of IL-1beta + tumor necrosis factor-alpha + interferon-gamma as well as functional suppression induced by the cytokine combination.
261	16751371	IL-1 is a key proinflammatory driver of several autoimmune diseases including juvenile inflammatory arthritis, diseases with mutations in the NALP/cryopyrin complex and Crohn's disease, and is genetically or clinically associated with many others.
262	16751371	Here we show that autoimmune-prone NOD and IL-1 receptor antagonist-deficient C57BL/6 mice both produce high levels of IL-1, which drives autoreactive effector cell expansion.
263	16751371	IL-1beta drives proliferation and cytokine production by CD4(+)CD25(+)FoxP3(-) effector/memory T cells, attenuates CD4(+)CD25(+)FoxP3(+) regulatory T cell function, and allows escape of CD4(+)CD25(-) autoreactive effectors from suppression.
264	16835316	Attractin, a dipeptidyl peptidase IV/CD26-like enzyme, is expressed on human peripheral blood monocytes and potentially influences monocyte function.
265	16835316	Moreover, this inhibitor significantly modulates the production of interleukin-1 (IL-1) receptor antagonist, IL-6, and transforming growth factor-beta1 in lipopolysaccharide-stimulated monocyte cultures.
266	17003335	Fas, a death receptor regulated by IL-1beta, is involved in glucose-induced beta-cell apoptosis.
267	17003335	Fas engagement can be switched from death signal to induction of proliferation when the caspase 8 inhibitor, FLICE-inhibitory protein (FLIP), is active.
268	17003335	A similarly bimodal induction of FLIP, pancreatic duodenal homeobox (PDX)-1, and Pax4 mRNA expression, as well as glucose-stimulated insulin secretion, was observed.
269	17003335	In contrast, Fas induction by IL-1beta was monophasic.
270	17003335	Low IL-1beta also induced the IL-1 receptor antagonist (IL-1Ra), suppression of which by RNA interference abrogated the beneficial effects of low IL-1beta.
271	17003335	Consistent with our in vitro results, IL-1beta knockout mice displayed glucose intolerance along with a decrease in islet Fas, FLIP, Pax4, and PDX-1 transcripts.
272	17003335	These findings indicate that low IL-1beta levels positively influence beta-cell function and turnover through the Fas-FLIP pathway and that IL-1Ra production prevents harmful effects of high IL-1beta concentrations.
273	17097645	IL-1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde?
274	17097645	Interleukin-1 receptor antagonist (IL-1ra) has been shown to play a crucial role in the prevention of various inflammatory diseases.
275	17097645	There is also convincing evidence that IL-1ra is able to counteract inflammatory effects of IL-1 members implicated in insulin resistance and diabetes.
276	17151292	The article examines the role of macrophages in autoimmune diabetes with particular emphasis on the role of galectin-3, a beta-galactoside-binding lectin, and T1/ST2, an IL-1 receptor-like protein, both of which play significant roles in the immunomodulatory functions of macrophages.
277	17151292	Deletion of the galectin-3 gene from C57BL/6 mice significantly attenuates this effect as evaluated by quantitative histology of mononuclear cells and loss of insulin-producing beta cells.
278	17175250	This study examined the combinatory effect on graft survival of neonatal pig pancreatic cell clusters (NPCC) with nordihydroguaiaretic acid (NDGA), a 5-lipoxygenase inhibitor, with systemic CTLA4Ig expression, with local CTLA4Ig and with interleukin-1 (IL-1) receptor antagonist (IL-1ra) expression using a pig to mouse model.
279	17267571	Importantly, recovery from the behavioral consequences of hypoxia-induced NSA was nearly ablated in MyD88 (myeloid differentiation factor 88) knock-out mice and in mice intracerebroventricularly administered the caspase-1 inhibitor ac-YVAD-CMK (ac-Tyr-Val-Asp-2,6-dimethylbenzoyloxymethylketone).
280	17267571	Diabetic mice had prolonged recovery from NSA that could be halved by administration of subcutaneous interleukin-1 (IL-1) receptor antagonist (RA).
281	17267571	These results show that acute hypoxia activates the IL-1beta arm of the neuroimmune system, which diabetes exacerbates and treatment with IL-1RA ameliorates.
282	17513737	Type 2 diabetes impairs insulin receptor substrate-2-mediated phosphatidylinositol 3-kinase activity in primary macrophages to induce a state of cytokine resistance to IL-4 in association with overexpression of suppressor of cytokine signaling-3.
283	17513737	In this study, we report that normal IL-4-dependent elaboration of IL-1 receptor antagonist (IL-1RA) requires IRS-2-mediated PI3K activity in primary macrophages.
284	17513737	We also show that macrophages isolated from obese/diabetic db/db mice have impaired IRS-2-mediated PI3K activity and constitutively overexpress suppressor of cytokine signaling (SOCS)-3, which impairs an important IL-4 anti-inflammatory function.
285	17513737	Resident peritoneal macrophages were isolated from db/db mice and were found to constitutively overexpress IL-6 and were unable to elaborate IL-1RA in response to IL-4-like db/+ mouse macrophages.
286	17513737	Inhibition of PI3K with wortmannin or blockage of IRS-2/PI3K complex formation with a cell permeable IRS-2-derived tyrosine phosphopeptide inhibited IL-4-dependent IL-1RA production in db/+ macrophages.
287	17513737	Examination of IL-4 signaling in db/db macrophages revealed that IL-4-dependent IRS-2/PI3K complex formation and IRS-2 tyrosine phosphorylation was reduced compared with db/+ macrophages.
288	17513737	SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression.
289	17513737	These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA.
290	18173174	[Interleukin 1 receptor antagonists prevent the induction of experimental insulin-dependent autoimmune diabetes].
291	18173174	During the induction of diabetes with multiple low-dose of streptozotocin (40-45 mg/kg body weigh for 5 consecutive days) starting from day 3, CBA mice were injected repeatedly (10 daily injections) with either rat IL-1 inhibitor (IL-1 INH) derived from glucocorticoid-treated macrophages, or with recombinant DNA produced human IL-1 receptor antagonist (rIL-1ra).
292	18173174	Our results, thus, suggest that IL-1 mediated immunopathogenic and/or inflammatory processes which lead to insulin-dependent diabetes, may be modulated by specific in vivo blockade of IL-1 receptors.
293	18191048	Weight reduction resulted in a decrease in the mRNA expression of IL-1beta (IL1B), IL-1 receptor antagonist, and tumor necrosis factor alpha (P < .001) and an increase in expression of IL-6 (IL6) and IL-8 (P < .01).
294	18191048	Interestingly, the decrease in IL1B expression was correlated with an increase in insulin sensitivity index (r = -0.68, P < .01).
295	18191048	The decrease in IL-1 receptor antagonist expression after weight loss and the strong correlation between the decrease in IL1B expression and the increase in insulin sensitivity suggest a contribution of these genes to insulin-resistant states found in obesity and the metabolic syndrome.
296	18191048	Weight reduction resulted in a decrease in the mRNA expression of IL-1beta (IL1B), IL-1 receptor antagonist, and tumor necrosis factor alpha (P < .001) and an increase in expression of IL-6 (IL6) and IL-8 (P < .01).
297	18191048	Interestingly, the decrease in IL1B expression was correlated with an increase in insulin sensitivity index (r = -0.68, P < .01).
298	18191048	The decrease in IL-1 receptor antagonist expression after weight loss and the strong correlation between the decrease in IL1B expression and the increase in insulin sensitivity suggest a contribution of these genes to insulin-resistant states found in obesity and the metabolic syndrome.
299	18239070	The antiinflammatory cytokine interleukin-1 receptor antagonist protects from high-fat diet-induced hyperglycemia.
300	18239070	A recent clinical trial shows that blocking IL-1beta signaling by IL-1 receptor antagonist (IL-1Ra) improves beta-cell secretory function in patients with type 2 diabetes.
301	18239070	IL-1Ra prevented diabetes in vivo in C57BL/6J mice fed a high-fat/high-sucrose diet (HFD) for 12 wk; it improved glucose tolerance and insulin secretion.
302	18239070	High-fat diet treatment increased serum levels of free fatty acids and of the adipokines resistin and leptin, which were reduced by IL-1Ra treatment.
303	18239070	In addition, IL-1Ra counteracted adiponectin levels, which were decreased by high-fat feeding.
304	18239070	IL-1Ra protected islets from HFD treated animals from beta-cell apoptosis, induced beta-cell proliferation, and improved glucose-stimulated insulin secretion.
305	18239070	Insulin mRNA was reduced in islets from mice fed a HFD but normalized in the IL-1Ra group.
306	19094928	Peroxisome proliferators activated receptors (PPAR) are ligand-inducible nuclear transacting factors comprising three subtypes, PPARalpha, PPARbeta/delta and PPARgamma, which play a key role in lipids and glucose homeostasis.
307	19094928	All PPAR subtypes have been identified in joint or inflammatory cells and their activation resulted in a transcriptional repression of pro-inflammatory cytokines (IL-1, TNFalpha), early inflammatory genes (NOS(2), COX-2, mPGES-1) or matrix metalloproteases (MMP-1, MMP-13), at least for the gamma subtype.
308	19094928	PPAR full agonists were also shown to stimulate IL-1 receptor antagonist (IL-1Ra) production by cytokine-stimulated articular cells in a subtype-dependent manner.
309	19094928	These anti-inflammatory and anti-catabolic properties were confirmed in animal models of joint diseases where PPAR agonists reduced synovial inflammation while preventing cartilage destruction or inflammatory bone loss, although many effects required much higher doses than needed to restore insulin sensitivity or to lower circulating lipid levels.
310	19094928	However, these promising effects of PPAR full agonists were hampered by their ability to reduce the growth factor-dependent synthesis of extracellular matrix components or to induce chondrocyte apoptosis, by the possible contribution of immunosuppressive properties to their anti-arthritic effects, by the increased adipocyte differentiation secondary to prolonged stimulation of PPARgamma, and by a variable contribution of PPAR subtypes depending on the system.
311	19399017	IL-1, a major proinflammatory cytokine, is present at increased levels in patients with diabetes mellitus, and could promote beta-cell destruction and alter insulin sensitivity.
312	19399017	The effects of IL-1 are likely to be counteracted by IL-1 receptor antagonist protein (IL-1ra), as suggested by interventional studies in patients with T2DM who were treated with a recombinant form of this protein.
313	19399017	However, studies in IL-1ra-deficient mice provided controversial results on the exact effect of the IL-1 signaling pathway on insulin secretion, insulin sensitivity and accumulation of adipose tissue.
314	19399017	Likewise, IL-6 has been suggested to be involved in the development of obesity-related and T2DM-related insulin resistance.
315	19541594	IL-1 receptor antagonism and muscle gene expression in patients with type 2 diabetes.
316	19666548	Specific blockade of IL-1 activity by the IL-1 receptor antagonist (IL-1Ra) reduced the release of inflammatory cytokines/chemokines from GK islets in vitro and from mouse islets exposed to metabolic stress.
317	19666548	Islets from mice deficient in IL-1beta or MyD88 challenged with glucose and palmitate in vitro also produced significantly less IL-6 and chemokines.
318	19666548	In addition, islet-derived proinflammatory cytokines/chemokines (IL-1beta, IL-6, TNFalpha, KC, MCP-1, and MIP-1alpha) and islet CD68(+), MHC II(+), and CD53(+) immune cell infiltration were reduced by IL-1Ra treatment.
319	19666548	Rather than being directly cytotoxic, IL-1beta may drive tissue inflammation that impacts on both beta cell functional mass and insulin sensitivity in type 2 diabetes.
320	19782393	We demonstrated that a poly(ethylene glycol)-containing hydrogel network, formed by native chemical ligation and presenting an inhibitory peptide for islet cell surface IL-1 receptor, was able to maintain the viability of encapsulated islet cells in the presence of a combination of cytokines including IL-1 beta, TNF-alpha, and INF-gamma.
321	19819943	Free fatty acids induce a proinflammatory response in islets via the abundantly expressed interleukin-1 receptor I.
322	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.
323	19819943	FFA induced IL-1beta, IL-6, and IL-8 in human islets and IL-1beta and KC in mouse islets.
324	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.
325	19845478	Interleukin-1 receptor antagonist (IL-1Ra) and IL-1Ra producing mesenchymal stem cells as modulators of diabetogenesis.
326	19845478	IL-1Ra is a naturally occurring cytokine and is the inhibitor of IL-1.
327	19845478	When IL-1Ra binds to the IL-1 receptor, binding of IL-1 is blocked by IL-1Ra and pro-inflammatory signal from IL-1 receptor is stopped.
328	19845478	There are mounting evidences to suggest that anti-inflammatory IL-1Ra reduces the inflammatory effects of IL-1 and preserves cell function in both types of diabetes.
329	19845478	IL-1Ra expressed by these MSCs effectively binds to IL-1 receptor and protects tissues from inflammation-induced injuries.
330	19845478	Interleukin-1 receptor antagonist (IL-1Ra) and IL-1Ra producing mesenchymal stem cells as modulators of diabetogenesis.
331	19845478	IL-1Ra is a naturally occurring cytokine and is the inhibitor of IL-1.
332	19845478	When IL-1Ra binds to the IL-1 receptor, binding of IL-1 is blocked by IL-1Ra and pro-inflammatory signal from IL-1 receptor is stopped.
333	19845478	There are mounting evidences to suggest that anti-inflammatory IL-1Ra reduces the inflammatory effects of IL-1 and preserves cell function in both types of diabetes.
334	19845478	IL-1Ra expressed by these MSCs effectively binds to IL-1 receptor and protects tissues from inflammation-induced injuries.
335	20074280	The role of the potent proinflammatory cytokine IL-1 in disease could clinically be investigated with the development of the IL-1 blocking agent anakinra (Kineret), a recombinant IL-1 receptor antagonist.
336	20074280	Recently the FDA approved two additional longer acting IL-1 blocking agents, for the treatment of cryopyrin-associated periodic syndromes (CAPS), an IL-1 dependent autoinflammatory syndrome.
337	20120526	Retinopathy and nephropathy in type 1 diabetic patients--association with polymorphysms of vitamin D-receptor, TNF, Neuro-D and IL-1 receptor 1 genes.
338	20120526	We genotyped variants in vitamin D receptor (VDR) and tumor necrosis factor (TNF) genes in 47 patients and in NeuroD1 and interleukin-1 receptor 1 (IL1R1) genes in 35 patients.
339	20177398	The effects of IL-1 are tightly controlled by several naturally occurring inhibitors, such as IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type II (IL-1RII), and other soluble receptors.
340	20177398	By contrast, the use of IL-1 antagonists has been uniformly associated with beneficial effects in patients with hereditary autoinflammatory conditions associated with excessive IL-1 signaling, such as cryopyrinopathies and IL-1Ra deficiency.
341	20460908	The pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are critically involved in the pathophysiology of various aspects of human NAFLD.
342	20460908	Serum levels of this cytokine correlate remarkably well with the presence of IR, and adipose tissue-derived IL-6 has been shown to regulate hepatic IR via upregulation of SOCS3.
343	20460908	Adiponectin is a potent TNF-alpha-neutralizing and anti-inflammatory adipocytokine, and in vitro and experimental animal studies have proven the importance of this mediator in counteracting inflammation and IR.
344	20460908	Anti-inflammatory effects of adiponectin are mediated via suppression of TNF-alpha synthesis as well as induction of anti-inflammatory cytokines such as IL-10 or IL-1 receptor antagonist.
345	20493414	Targeting IL-1beta in disease; the expanding role of NLRP3 inflammasome.
346	20493414	NLRP3 inflammasome activation and IL-1beta secretion have recently emerged as a central mechanism in the pathogenesis of disease.
347	20493414	Genetically defined syndromes like cryopyrin-associated periodic syndromes (CAPS, cryopyrinopathies) and familial Mediterranean fever (FMF) or diseases associated with NLRP3 activation by danger signals like gout, pseudogout, Alzheimer's disease or type 2 diabetes are included in this group of diseases.
348	20493414	The contribution of anakinra, a recombinant, nonglycosylated human IL-1 receptor antagonist, in both the identification and treatment of such syndromes was considerable.
349	20493414	Recently, rilonacept, a long-acting IL-1 receptor fusion protein, and canakinumab, a fully humanized anti-IL-1beta monoclonal antibody, have been developed, with the intention to further extent IL-1beta inhibition treatment strategies to a broader spectrum of disorders beyond the characterized autoinflammatory syndromes, offering a more favorable administration profile.
350	20493414	Targeting IL-1beta in disease; the expanding role of NLRP3 inflammasome.
351	20493414	NLRP3 inflammasome activation and IL-1beta secretion have recently emerged as a central mechanism in the pathogenesis of disease.
352	20493414	Genetically defined syndromes like cryopyrin-associated periodic syndromes (CAPS, cryopyrinopathies) and familial Mediterranean fever (FMF) or diseases associated with NLRP3 activation by danger signals like gout, pseudogout, Alzheimer's disease or type 2 diabetes are included in this group of diseases.
353	20493414	The contribution of anakinra, a recombinant, nonglycosylated human IL-1 receptor antagonist, in both the identification and treatment of such syndromes was considerable.
354	20493414	Recently, rilonacept, a long-acting IL-1 receptor fusion protein, and canakinumab, a fully humanized anti-IL-1beta monoclonal antibody, have been developed, with the intention to further extent IL-1beta inhibition treatment strategies to a broader spectrum of disorders beyond the characterized autoinflammatory syndromes, offering a more favorable administration profile.
355	21205020	Associations between interleukin-1 (IL-1) gene variations or IL-1 receptor antagonist levels and the development of type 2 diabetes.
356	21237203	Isolated islets from both strains were exposed to human IL-1β (25U/ml) or a combination of human IL-1β (25U/ml) and murine IFN-γ (1000U/ml) for 24h or 48h and we investigated the expression of IL-1 receptor antagonist (IL-1Ra) mRNA in islet cells and secretion of IL-1Ra into culture medium.
357	21237203	Exposure of wt islets to IL-1β or IL-1β+IFN-γ seemed to lead to a failing IL-1Ra response from SOCS-3 transgenic islets.
358	21393239	Neutralizing interleukin-1beta (IL-1beta) induces beta-cell survival by maintaining PDX1 protein nuclear localization.
359	21393239	The transcription factor PDX1 plays a critical role during β-cell development and in glucose-induced insulin gene transcription in adult β-cells.
360	21393239	In isolated islets from patients with type 2 diabetes and from diabetic mice, we found opposite regulation of insulin and PDX1 mRNA; insulin was decreased in diabetes, but PDX1 was increased.
361	21393239	This suggests that elevated PDX1 mRNA levels may be insufficient to regulate insulin.
362	21393239	In contrast, overexpression of either IL-1 receptor antagonist or shuttling-deficient PDX1 restored β-cell survival and function and PDX1 nuclear localization.
363	21393239	Our results show that nuclear localization of PDX1 is essential for a functional β-cell and provides a novel mechanism of the protective effect of IL-1 receptor antagonist on β-cell survival and function.
364	21393239	Neutralizing interleukin-1beta (IL-1beta) induces beta-cell survival by maintaining PDX1 protein nuclear localization.
365	21393239	The transcription factor PDX1 plays a critical role during β-cell development and in glucose-induced insulin gene transcription in adult β-cells.
366	21393239	In isolated islets from patients with type 2 diabetes and from diabetic mice, we found opposite regulation of insulin and PDX1 mRNA; insulin was decreased in diabetes, but PDX1 was increased.
367	21393239	This suggests that elevated PDX1 mRNA levels may be insufficient to regulate insulin.
368	21393239	In contrast, overexpression of either IL-1 receptor antagonist or shuttling-deficient PDX1 restored β-cell survival and function and PDX1 nuclear localization.
369	21393239	Our results show that nuclear localization of PDX1 is essential for a functional β-cell and provides a novel mechanism of the protective effect of IL-1 receptor antagonist on β-cell survival and function.
370	21700474	PPARγ agonist rosiglitazone ameliorates LPS-induced inflammation in vascular smooth muscle cells via the TLR4/TRIF/IRF3/IP-10 signaling pathway.
371	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.
372	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).
373	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.
374	22043003	To test this, we treated hyperglycemic NOD mice with F(ab')(2) fragments of anti-CD3 mAb with or without IL-1 receptor antagonist (IL-1RA), or anti-IL-1β mAb.
375	22043003	Combination-treated mice had increased IL-5, IL-4, and interferon (IFN)-γ levels in circulation.
376	22043003	After 1 month, there were increased concentrations of IgG1 isotype antibodies and reduced intrapancreatic expression of IFN-γ, IL-6, and IL-17 despite normal splenocyte cytokine secretion.
377	22075986	The identification of the underlying mechanism in these disorders has led to their now successful therapy, with the use of the IL-1 receptor antagonist in the clinic.
378	22506644	Targeting the IL-1 system with the IL-1 receptor antagonist IL1Ra improved insulin secretion, glycaemia and reduced systemic inflammation in a proof of concept study with patients with type 2 diabetes.
379	22521751	Interleukin-1 (IL-1) family of cytokines: role in type 2 diabetes.
380	22521751	Virtually all nucleated cells, especially endo/epithelial cells and macrophages are potent producers of IL-1, IL-6 and TNF-α.
381	22521751	The IL-1 family consists of two pro-inflammatory cytokines, IL-1α and IL-1β, and a naturally occurring anti-inflammatory agent, the IL-1 receptor antagonist (IL-1Ra or IL-1RN).
382	22634722	An increasing amount of evidence appears to suggest that AAT possesses not only the ability to inhibit serine proteases, such as elastase and proteinase-3 (PR-3), but also to exert antiinflammatory and tissue-protective effects independent of protease inhibition.
383	22634722	AAT modifies dendritic cell maturation and promotes T regulatory cell differentiation, induces interleukin (IL)-1 receptor antagonist and IL-10 release, protects various cell types from cell death, inhibits caspases-1 and -3 activity and inhibits IL-1 production and activity.
384	22707198	Microarray data demonstrated for the first time that overexpression of the genes encoding IL-1 receptor, lipid metabolic enzymes (e.g.
385	22707198	Mte1, Ptdss1, and Sult2a1), myo-inositol oxygenase, glucagon, and somatostatin as well as down-regulation of olfactory receptor 984 and mitochondrial ribosomal protein, which are highly linked to T1DM etiology.
386	22707198	The results of the microarray analysis revealed that up-regulation of IL-2, IL12a, and leptin receptor and down-regulation of PIK3 played important physiological roles in the onset of T2DM.
387	23195532	IL-1 receptor 2 (IL-1R2) and its role in immune regulation.
388	23195532	The functional significance of IL-1 receptor antagonist (IL-1RA) is well documented due to the clinical utilization of the recombinant human IL-1RA analog, anakinra.
389	23195532	In contrast, much less is known about the type 2 IL-1 receptor (IL-1R2), which acts as a decoy receptor for IL-1.
390	23195532	While IL-1R2 is structurally similar to the type 1 IL-1 receptor (IL-1R1) responsible for IL-1 signal transduction, its truncated cytoplasmic domain and lack of Toll-IL-1 receptor (TIR) region renders IL-1R2 incapable of transmembrane signaling.
391	23195532	IL-1R2 competes with IL-1R1 for ligands and for the IL-1R1 co-receptor, IL-1 receptor accessory protein (IL-1RAP).
392	23195532	IL-1 receptor 2 (IL-1R2) and its role in immune regulation.
393	23195532	The functional significance of IL-1 receptor antagonist (IL-1RA) is well documented due to the clinical utilization of the recombinant human IL-1RA analog, anakinra.
394	23195532	In contrast, much less is known about the type 2 IL-1 receptor (IL-1R2), which acts as a decoy receptor for IL-1.
395	23195532	While IL-1R2 is structurally similar to the type 1 IL-1 receptor (IL-1R1) responsible for IL-1 signal transduction, its truncated cytoplasmic domain and lack of Toll-IL-1 receptor (TIR) region renders IL-1R2 incapable of transmembrane signaling.
396	23195532	IL-1R2 competes with IL-1R1 for ligands and for the IL-1R1 co-receptor, IL-1 receptor accessory protein (IL-1RAP).
397	23195532	IL-1 receptor 2 (IL-1R2) and its role in immune regulation.
398	23195532	The functional significance of IL-1 receptor antagonist (IL-1RA) is well documented due to the clinical utilization of the recombinant human IL-1RA analog, anakinra.
399	23195532	In contrast, much less is known about the type 2 IL-1 receptor (IL-1R2), which acts as a decoy receptor for IL-1.
400	23195532	While IL-1R2 is structurally similar to the type 1 IL-1 receptor (IL-1R1) responsible for IL-1 signal transduction, its truncated cytoplasmic domain and lack of Toll-IL-1 receptor (TIR) region renders IL-1R2 incapable of transmembrane signaling.
401	23195532	IL-1R2 competes with IL-1R1 for ligands and for the IL-1R1 co-receptor, IL-1 receptor accessory protein (IL-1RAP).
402	23195532	IL-1 receptor 2 (IL-1R2) and its role in immune regulation.
403	23195532	The functional significance of IL-1 receptor antagonist (IL-1RA) is well documented due to the clinical utilization of the recombinant human IL-1RA analog, anakinra.
404	23195532	In contrast, much less is known about the type 2 IL-1 receptor (IL-1R2), which acts as a decoy receptor for IL-1.
405	23195532	While IL-1R2 is structurally similar to the type 1 IL-1 receptor (IL-1R1) responsible for IL-1 signal transduction, its truncated cytoplasmic domain and lack of Toll-IL-1 receptor (TIR) region renders IL-1R2 incapable of transmembrane signaling.
406	23195532	IL-1R2 competes with IL-1R1 for ligands and for the IL-1R1 co-receptor, IL-1 receptor accessory protein (IL-1RAP).
407	23195532	IL-1 receptor 2 (IL-1R2) and its role in immune regulation.
408	23195532	The functional significance of IL-1 receptor antagonist (IL-1RA) is well documented due to the clinical utilization of the recombinant human IL-1RA analog, anakinra.
409	23195532	In contrast, much less is known about the type 2 IL-1 receptor (IL-1R2), which acts as a decoy receptor for IL-1.
410	23195532	While IL-1R2 is structurally similar to the type 1 IL-1 receptor (IL-1R1) responsible for IL-1 signal transduction, its truncated cytoplasmic domain and lack of Toll-IL-1 receptor (TIR) region renders IL-1R2 incapable of transmembrane signaling.
411	23195532	IL-1R2 competes with IL-1R1 for ligands and for the IL-1R1 co-receptor, IL-1 receptor accessory protein (IL-1RAP).
412	23460390	Interleukin-1 (IL-1)-mediated diseases are caused by an inappropriately high production and release of IL-1 beta which results in a multitude of symptoms, e.g. arthritis, exanthema, conjunctivitis, serositis, fever and loss of hearing.
413	23460390	These diseases often manifesting in childhood can now be treated with monoclonal antibodies against IL-1 or with IL-1 receptor antagonists.
414	23460390	Increased IL-1 secretion does not only play a role in relatively rare hereditary diseases, such as cryopyrin-associated periodic fever syndromes or familial Mediterranean fever but also in widespread diseases, such as gout or type 2 diabetes.
415	23493576	Furthermore, inhibiting the IL-1β pathway using a neutralizing antibody and macrophages from IL-1 receptor knockout mice blocked the conditioned medium-induced upregulation of proinflammatory genes and downregulation of prohealing factors.
416	23664771	We previously reported that IL-1 Trap (a hybrid molecule consisting of the extracellular domain of IL-1 receptor accessory protein and IL-1 receptor type 1 arranged inline and fused to the Fc-portion of IgG1) can protect rat pancreatic islets in vitro against noxious effects induced by IL-1β.
417	23664771	The treatments were maintained until ROD (i.e. a blood glucose value ⩾11.1mM for 2 consecutive days) or until 5days after transplantation. 3 out of 11 mice treated with IL-1 Trap showed a significantly increased graft survival compared to all other mice, and analysis of relative cytokine mRNA levels in isolated spleen cells showed elevated IL-4 mRNA levels, but no differences in FoxP3 or iNOS staining of grafts, from mice treated with IL-1 Trap, at both endpoints, compared to both control groups.
418	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.
419	23921144	We also observed that PA augmented TLR4 but not TLR2 signal, and the augmentation was mediated by nuclear factor-κB (NF-κB) pathways.
420	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.