Ignet

Gene Information

Gene symbol: CASP1

Gene name: caspase 1, apoptosis-related cysteine peptidase

HGNC ID: 1499

Synonyms: ICE

Related Genes

#	Gene Symbol	Number of hits
1	ADIPOQ	1 hits
2	AIFM1	1 hits
3	AIM2	1 hits
4	AKTIP	1 hits
5	APLP2	1 hits
6	BCL2	1 hits
7	BCL2L1	1 hits
8	CARD8	1 hits
9	CASP3	1 hits
10	CASP8	1 hits
11	CAT	1 hits
12	CD4	1 hits
13	CYCS	1 hits
14	FADD	1 hits
15	FAS	1 hits
16	FASLG	1 hits
17	GSTCD	1 hits
18	HSPA1A	1 hits
19	IAPP	1 hits
20	ICAM1	1 hits
21	IFNG	1 hits
22	IL10	1 hits
23	IL15	1 hits
24	IL18	1 hits
25	IL1A	1 hits
26	IL1B	1 hits
27	IL33	1 hits
28	IL6	1 hits
29	INS	1 hits
30	JUN	1 hits
31	LEP	1 hits
32	LGALS3	1 hits
33	MAFA	1 hits
34	MAPK8	1 hits
35	MEFV	1 hits
36	MYD88	1 hits
37	NFKB1	1 hits
38	NFKBIA	1 hits
39	NIT1	1 hits
40	NLRC4	1 hits
41	NLRP1	1 hits
42	NLRP12	1 hits
43	NLRP3	1 hits
44	NOS2A	1 hits
45	P2RX2	1 hits
46	P2RX4	1 hits
47	PDX1	1 hits
48	PTGS2	1 hits
49	PYCARD	1 hits
50	PYDC1	1 hits
51	REN	1 hits
52	SIRT1	1 hits
53	SLURP1	1 hits
54	SOD2	1 hits
55	TNF	1 hits
56	TXNIP	1 hits
57	VEGFA	1 hits

Related Sentences

#	PMID	Sentence
1	7027249	Insulin-containing erythrocyte (ICE) number was reduced in patients with an evident form of diabetes mellitus and in 50% of patients of the 2nd group (less than 60%).
2	7439544	The 24-h integrated plasma concentration of glucose (IC-glucose), norepinephrine (IC-NE), epinephrine (IC-E), cortisol (IC-F), growth hormone (IC-GH), aldosterone (IC-ALDO), and plasma renin activity (IC-PRA) were measured in 11 nonobese juvenile-onset nonketotic diabetic patients exhibiting hyperglycemia and glycosuria and 34 matched control subjects using a portable pump, drawing blood at a constant rate through a nonthrombogenic i.v. catheter.
3	8613527	Chronic exposure of betaTC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator.
4	8613527	We have shown previously that chronic exposure of HIT-T15 cells to supraphysiologic glucose concentrations causes decreased insulin gene transcription and decreased binding activities of two beta-cell specific transcription factors, STF-1 and the RIPE3b1 activator, and have suggested that these events may provide a mechanism for glucose toxicity on beta-cell function.
5	8613527	Electromobility shift assays demonstrated that binding of a specific nuclear protein that recognizes the RIPE3b1 binding site of the insulin gene was markedly diminished in late passage cells chronically exposed to 11.1 mM glucose, whereas binding activities of STF-1 and ICE activators were unchanged.
6	8613527	Mutation of the RIPE3b1 binding site almost completely abolished insulin gene transcription as well as binding activity.
7	8613527	We conclude that chronic exposure of betaTC-6 cells to high glucose concentrations paradoxically decreases insulin gene transcription, in part, by decreasing activity of the trans-activating factor which binds to the RIPE3b1 sequence.
8	8613527	This study uniquely demonstrates that altered binding to the RIPE3b1 sequence mediates glucose toxicity in betaTC-6 cells, thus reinforcing the importance of this cis-acting element in the regulation of insulin gene transcription.
9	9218757	Protection of NIT-1 pancreatic beta-cells from immune attack by inhibition of NF-kappaB.
10	9218757	We have recently observed that inhibition of NF-kappaB in NIT-1 insulinoma cells protects them from tumour necrosis factor (TNF)-induced cell death in vitro, possibly because expression of interleukin-1 (IL-1)beta-converting enzyme (ICE), a member of the cysteine protease pathway of cell death, is decreased.
11	9218757	In the current study we have examined the effect of the same inhibitor of NF-kappaB on class I major histocompatibility complex (MHC) protein expression in NIT-1 cells and shown that inhibition of NF-kappaB activation decreased basal and TNF-induced class I MHC levels.
12	9218757	Although inducible nitric oxide synthase (iNOS) may also be inhibited by inhibition of NF-kappaB, this could not be demonstrated in NIT-1/delta sp cells because wild-type NIT-1 cells express very little iNOS.
13	9218757	When NIT-1/delta sp12 cells, expressing high levels of the NF-kappaB inhibitor, are transplanted into immunodeficient NOD/scid mice, tumorigenesis and death by hypoglycemia proceed similarly to untransfected NIT-1 cells.
14	9218757	In conclusion, inhibition of NF-kappaB is likely to suppress several different pathways of immune-mediated cell death in beta-cells and protects NIT-1 cells from immune attack by diabetogenic T cells in vivo.
15	9783328	Moreover, immunoblot analysis showed high Bcl-2 and undetectable caspase-1 levels in embryos from both normal and diabetic rats and low Bcl-2 and high caspase-1 levels in the corresponding yolk sacs.
16	9840679	Islet expression of perforin, Fas/Apo-1 and interleukin-1 converting enzyme (ICE) in non-obese diabetic (NOD) mice.
17	9840679	The aim of the present study was to correlate the islet expression of the apoptosis-associated factors Fas/Apo-1, FasL, ICE and perforin with the progression of beta-cell destruction in non-obese diabetic (NOD) mice.
18	9840679	Islet expression of the Fas/Apo-1 receptor and ICE were increased in islets from female mice 15 weeks of age as compared to corresponding males.
19	9840679	No Fas/Apo-1 or ICE signal was observed in the 5-week-old mice.
20	9840679	Culture of isolated islets from NMRI mice in the presence of interleukin-1beta (IL-1beta) induced the expression of ICE.
21	9840679	The present results support a direct role of the Fas/FasL and the perforin systems in the autoimmune destruction of insulin producing cells [corrected].
22	9840679	Islet expression of perforin, Fas/Apo-1 and interleukin-1 converting enzyme (ICE) in non-obese diabetic (NOD) mice.
23	9840679	The aim of the present study was to correlate the islet expression of the apoptosis-associated factors Fas/Apo-1, FasL, ICE and perforin with the progression of beta-cell destruction in non-obese diabetic (NOD) mice.
24	9840679	Islet expression of the Fas/Apo-1 receptor and ICE were increased in islets from female mice 15 weeks of age as compared to corresponding males.
25	9840679	No Fas/Apo-1 or ICE signal was observed in the 5-week-old mice.
26	9840679	Culture of isolated islets from NMRI mice in the presence of interleukin-1beta (IL-1beta) induced the expression of ICE.
27	9840679	The present results support a direct role of the Fas/FasL and the perforin systems in the autoimmune destruction of insulin producing cells [corrected].
28	9840679	Islet expression of perforin, Fas/Apo-1 and interleukin-1 converting enzyme (ICE) in non-obese diabetic (NOD) mice.
29	9840679	The aim of the present study was to correlate the islet expression of the apoptosis-associated factors Fas/Apo-1, FasL, ICE and perforin with the progression of beta-cell destruction in non-obese diabetic (NOD) mice.
30	9840679	Islet expression of the Fas/Apo-1 receptor and ICE were increased in islets from female mice 15 weeks of age as compared to corresponding males.
31	9840679	No Fas/Apo-1 or ICE signal was observed in the 5-week-old mice.
32	9840679	Culture of isolated islets from NMRI mice in the presence of interleukin-1beta (IL-1beta) induced the expression of ICE.
33	9840679	The present results support a direct role of the Fas/FasL and the perforin systems in the autoimmune destruction of insulin producing cells [corrected].
34	9840679	Islet expression of perforin, Fas/Apo-1 and interleukin-1 converting enzyme (ICE) in non-obese diabetic (NOD) mice.
35	9840679	The aim of the present study was to correlate the islet expression of the apoptosis-associated factors Fas/Apo-1, FasL, ICE and perforin with the progression of beta-cell destruction in non-obese diabetic (NOD) mice.
36	9840679	Islet expression of the Fas/Apo-1 receptor and ICE were increased in islets from female mice 15 weeks of age as compared to corresponding males.
37	9840679	No Fas/Apo-1 or ICE signal was observed in the 5-week-old mice.
38	9840679	Culture of isolated islets from NMRI mice in the presence of interleukin-1beta (IL-1beta) induced the expression of ICE.
39	9840679	The present results support a direct role of the Fas/FasL and the perforin systems in the autoimmune destruction of insulin producing cells [corrected].
40	9840679	Islet expression of perforin, Fas/Apo-1 and interleukin-1 converting enzyme (ICE) in non-obese diabetic (NOD) mice.
41	9840679	The aim of the present study was to correlate the islet expression of the apoptosis-associated factors Fas/Apo-1, FasL, ICE and perforin with the progression of beta-cell destruction in non-obese diabetic (NOD) mice.
42	9840679	Islet expression of the Fas/Apo-1 receptor and ICE were increased in islets from female mice 15 weeks of age as compared to corresponding males.
43	9840679	No Fas/Apo-1 or ICE signal was observed in the 5-week-old mice.
44	9840679	Culture of isolated islets from NMRI mice in the presence of interleukin-1beta (IL-1beta) induced the expression of ICE.
45	9840679	The present results support a direct role of the Fas/FasL and the perforin systems in the autoimmune destruction of insulin producing cells [corrected].
46	10078546	Essential role of caspase-3 in apoptosis of mouse beta-cells transfected with human Fas.
47	10078546	The cross-linking of Fas by anti-Fas resulted in the elevation of caspase-3-like, but not caspase-1-like, protease activity 2-12 h after the addition of the anti-Fas.
48	10078546	A caspase-3 inhibitor, Z-Asp-Glu-Val-Asp-fluoromethyl ketone, attenuated the Fas-mediated beta-cell apoptosis, while a caspase-1 inhibitor, acetyl-Tyr-Val-Ala-Asp-chloromethylketone, failed to suppress the apoptosis.
49	10078546	Furthermore, an antisense caspase-3 construct blocked caspase-3 activation and substantially suppressed Fas-triggered apoptosis of hFas/betaTC1 cells.
50	10078546	Essential role of caspase-3 in apoptosis of mouse beta-cells transfected with human Fas.
51	10078546	The cross-linking of Fas by anti-Fas resulted in the elevation of caspase-3-like, but not caspase-1-like, protease activity 2-12 h after the addition of the anti-Fas.
52	10078546	A caspase-3 inhibitor, Z-Asp-Glu-Val-Asp-fluoromethyl ketone, attenuated the Fas-mediated beta-cell apoptosis, while a caspase-1 inhibitor, acetyl-Tyr-Val-Ala-Asp-chloromethylketone, failed to suppress the apoptosis.
53	10078546	Furthermore, an antisense caspase-3 construct blocked caspase-3 activation and substantially suppressed Fas-triggered apoptosis of hFas/betaTC1 cells.
54	10099840	Total mRNA of the purified pericytes was isolated for quantitative reverse transcriptase (RT)-PCR assay. mRNA levels of a death protease (CPP32), the major enzyme that initiates the proteolytic cascade leading to cell death, were determined in association with the expression of antioxidative enzymes including glutathione peroxidase (GSH-Px), glutathione reductase, CuZn superoxide dismutase (SOD), MnSOD and catalase genes in pericytes.
55	10099840	In diabetic pericytes, up-regulation of glutathione peroxidase (GSH-Px) (8.2 +/- 0.9 fold increase, p < 0.01, n = 9) and down-regulation of glutathione reductase (Gr) (4.1 +/- 0.4 fold decrease, p < 0.05, n = 9) and CuZnSOD (2.1 +/- 0.7 fold decrease, p < 0.05, n = 9) were observed. mRNA levels of MnSOD and catalase of diabetic pericytes did not differ significantly from those of non-diabetic pericytes.
56	10099840	Overexpression of a member of interleukin-1 beta-converting enzyme (ICE) family, CPP32, indicated that the pericytes from diabetic retinas are in a "pre-PCD" state.
57	10385418	Tumor necrosis factor-alpha (TNFalpha) is a potential mediator of beta cell destruction in insulin-dependent diabetes mellitus.
58	10385418	Primary beta cells express low levels of the type I TNF receptor (TNFR1) but do not express the type 2 receptor (TNFR2).
59	10385418	Evidence for TNFR1 expression on beta cells came from flow cytometry using monoclonal antibodies specific for TNFR1 and TNFR2 and from RT-PCR of beta cell RNA.
60	10385418	TNF induced NF-kappaB activation in both primary islet cells and NIT-1 cells.
61	10385418	Apoptosis in response to TNFalpha was observed in NIT-1 cells whereas apoptosis of primary beta cells required both TNFalpha and interferon-gamma (IFNgamma).
62	10385418	Apoptosis could be prevented in NIT-1 cells by expression of dominant negative Fas-associating protein with death domain (dnFADD).
63	10385418	Apoptosis in NIT-1 cells was increased by coincubation with IFNgamma, which also increased caspase 1 expression.
64	10385418	Caspase activation is the dominant pathway of TNF-induced cell death in NIT-1 cells and may be an important mechanism of beta cell damage in insulin-dependent diabetes mellitus.
65	10690898	Interferon-gamma induces interleukin-1 converting enzyme expression in pancreatic islets by an interferon regulatory factor-1-dependent mechanism.
66	10690898	The cysteine protease interleukin (IL)-1 converting enzyme (ICE) is a key proapoptotic caspase.
67	10690898	ICE messenger RNA (mRNA) expression was highly up-regulated after 6-, 24-, and 72-h exposure of human islets to interferon (IFN)gamma, tumor necrosis factor (TNF)alpha + IFNgamma or IL-1beta + TNFalpha + IFNgamma, paralleled by increased iNOS (the inducible form of NO synthase) expression and NO production after exposure to the combined cytokines but not to IFNgamma or TNFalpha + IFNgamma.
68	10690898	Cytokine-induced NO-independent ICE transcription was confirmed using iNOS inhibitors.
69	10690898	Exposure of rat and mouse islets, or rat insulinoma cells, for 24 h to IFNgamma alone or in combination with the two other cytokines also resulted in a highly significant ICE mRNA expression.
70	10690898	ICE transcription was not inducible in islets from IFN regulatory factor-1 knock-out mice, suggesting a key-role of this transcription-factor in cytokine-mediated ICE expression in pancreatic islets.
71	10690898	In conclusion, cytokines and IFNgamma in particular increase ICE mRNA expression in pancreatic islet cells and beta-cell lines, independently of NO synthesis, suggesting that ICE up-regulation may be involved in cytokine-induced NO-independent apoptosis of human islets.
72	10690898	Interferon-gamma induces interleukin-1 converting enzyme expression in pancreatic islets by an interferon regulatory factor-1-dependent mechanism.
73	10690898	The cysteine protease interleukin (IL)-1 converting enzyme (ICE) is a key proapoptotic caspase.
74	10690898	ICE messenger RNA (mRNA) expression was highly up-regulated after 6-, 24-, and 72-h exposure of human islets to interferon (IFN)gamma, tumor necrosis factor (TNF)alpha + IFNgamma or IL-1beta + TNFalpha + IFNgamma, paralleled by increased iNOS (the inducible form of NO synthase) expression and NO production after exposure to the combined cytokines but not to IFNgamma or TNFalpha + IFNgamma.
75	10690898	Cytokine-induced NO-independent ICE transcription was confirmed using iNOS inhibitors.
76	10690898	Exposure of rat and mouse islets, or rat insulinoma cells, for 24 h to IFNgamma alone or in combination with the two other cytokines also resulted in a highly significant ICE mRNA expression.
77	10690898	ICE transcription was not inducible in islets from IFN regulatory factor-1 knock-out mice, suggesting a key-role of this transcription-factor in cytokine-mediated ICE expression in pancreatic islets.
78	10690898	In conclusion, cytokines and IFNgamma in particular increase ICE mRNA expression in pancreatic islet cells and beta-cell lines, independently of NO synthesis, suggesting that ICE up-regulation may be involved in cytokine-induced NO-independent apoptosis of human islets.
79	10690898	Interferon-gamma induces interleukin-1 converting enzyme expression in pancreatic islets by an interferon regulatory factor-1-dependent mechanism.
80	10690898	The cysteine protease interleukin (IL)-1 converting enzyme (ICE) is a key proapoptotic caspase.
81	10690898	ICE messenger RNA (mRNA) expression was highly up-regulated after 6-, 24-, and 72-h exposure of human islets to interferon (IFN)gamma, tumor necrosis factor (TNF)alpha + IFNgamma or IL-1beta + TNFalpha + IFNgamma, paralleled by increased iNOS (the inducible form of NO synthase) expression and NO production after exposure to the combined cytokines but not to IFNgamma or TNFalpha + IFNgamma.
82	10690898	Cytokine-induced NO-independent ICE transcription was confirmed using iNOS inhibitors.
83	10690898	Exposure of rat and mouse islets, or rat insulinoma cells, for 24 h to IFNgamma alone or in combination with the two other cytokines also resulted in a highly significant ICE mRNA expression.
84	10690898	ICE transcription was not inducible in islets from IFN regulatory factor-1 knock-out mice, suggesting a key-role of this transcription-factor in cytokine-mediated ICE expression in pancreatic islets.
85	10690898	In conclusion, cytokines and IFNgamma in particular increase ICE mRNA expression in pancreatic islet cells and beta-cell lines, independently of NO synthesis, suggesting that ICE up-regulation may be involved in cytokine-induced NO-independent apoptosis of human islets.
86	10690898	Interferon-gamma induces interleukin-1 converting enzyme expression in pancreatic islets by an interferon regulatory factor-1-dependent mechanism.
87	10690898	The cysteine protease interleukin (IL)-1 converting enzyme (ICE) is a key proapoptotic caspase.
88	10690898	ICE messenger RNA (mRNA) expression was highly up-regulated after 6-, 24-, and 72-h exposure of human islets to interferon (IFN)gamma, tumor necrosis factor (TNF)alpha + IFNgamma or IL-1beta + TNFalpha + IFNgamma, paralleled by increased iNOS (the inducible form of NO synthase) expression and NO production after exposure to the combined cytokines but not to IFNgamma or TNFalpha + IFNgamma.
89	10690898	Cytokine-induced NO-independent ICE transcription was confirmed using iNOS inhibitors.
90	10690898	Exposure of rat and mouse islets, or rat insulinoma cells, for 24 h to IFNgamma alone or in combination with the two other cytokines also resulted in a highly significant ICE mRNA expression.
91	10690898	ICE transcription was not inducible in islets from IFN regulatory factor-1 knock-out mice, suggesting a key-role of this transcription-factor in cytokine-mediated ICE expression in pancreatic islets.
92	10690898	In conclusion, cytokines and IFNgamma in particular increase ICE mRNA expression in pancreatic islet cells and beta-cell lines, independently of NO synthesis, suggesting that ICE up-regulation may be involved in cytokine-induced NO-independent apoptosis of human islets.
93	10690898	Interferon-gamma induces interleukin-1 converting enzyme expression in pancreatic islets by an interferon regulatory factor-1-dependent mechanism.
94	10690898	The cysteine protease interleukin (IL)-1 converting enzyme (ICE) is a key proapoptotic caspase.
95	10690898	ICE messenger RNA (mRNA) expression was highly up-regulated after 6-, 24-, and 72-h exposure of human islets to interferon (IFN)gamma, tumor necrosis factor (TNF)alpha + IFNgamma or IL-1beta + TNFalpha + IFNgamma, paralleled by increased iNOS (the inducible form of NO synthase) expression and NO production after exposure to the combined cytokines but not to IFNgamma or TNFalpha + IFNgamma.
96	10690898	Cytokine-induced NO-independent ICE transcription was confirmed using iNOS inhibitors.
97	10690898	Exposure of rat and mouse islets, or rat insulinoma cells, for 24 h to IFNgamma alone or in combination with the two other cytokines also resulted in a highly significant ICE mRNA expression.
98	10690898	ICE transcription was not inducible in islets from IFN regulatory factor-1 knock-out mice, suggesting a key-role of this transcription-factor in cytokine-mediated ICE expression in pancreatic islets.
99	10690898	In conclusion, cytokines and IFNgamma in particular increase ICE mRNA expression in pancreatic islet cells and beta-cell lines, independently of NO synthesis, suggesting that ICE up-regulation may be involved in cytokine-induced NO-independent apoptosis of human islets.
100	10690898	Interferon-gamma induces interleukin-1 converting enzyme expression in pancreatic islets by an interferon regulatory factor-1-dependent mechanism.
101	10690898	The cysteine protease interleukin (IL)-1 converting enzyme (ICE) is a key proapoptotic caspase.
102	10690898	ICE messenger RNA (mRNA) expression was highly up-regulated after 6-, 24-, and 72-h exposure of human islets to interferon (IFN)gamma, tumor necrosis factor (TNF)alpha + IFNgamma or IL-1beta + TNFalpha + IFNgamma, paralleled by increased iNOS (the inducible form of NO synthase) expression and NO production after exposure to the combined cytokines but not to IFNgamma or TNFalpha + IFNgamma.
103	10690898	Cytokine-induced NO-independent ICE transcription was confirmed using iNOS inhibitors.
104	10690898	Exposure of rat and mouse islets, or rat insulinoma cells, for 24 h to IFNgamma alone or in combination with the two other cytokines also resulted in a highly significant ICE mRNA expression.
105	10690898	ICE transcription was not inducible in islets from IFN regulatory factor-1 knock-out mice, suggesting a key-role of this transcription-factor in cytokine-mediated ICE expression in pancreatic islets.
106	10690898	In conclusion, cytokines and IFNgamma in particular increase ICE mRNA expression in pancreatic islet cells and beta-cell lines, independently of NO synthesis, suggesting that ICE up-regulation may be involved in cytokine-induced NO-independent apoptosis of human islets.
107	11108714	In combination, synthetic dsRNA (polyinosinic-polycytidylic acid, poly(I-C)) and interferon (IFN)-gamma stimulate inducible nitric-oxide synthase (iNOS) expression, inhibit insulin secretion, and induce islet degeneration.
108	11108714	Interleukin-1 (IL-1) appears to mediate dsRNA + IFN-gamma-induced islet damage in a nitric oxide-dependent manner, as the interleukin-1 receptor antagonist protein prevents dsRNA + IFN-gamma-induced iNOS expression, inhibition of insulin secretion, and islet degeneration.
109	11108714	IL-1beta is synthesized as an inactive precursor protein that requires cleavage by the IL-1beta-converting enzyme (ICE) for activation. dsRNA and IFN-gamma stimulate IL-1beta expression and ICE activation in primary beta-cells, respectively.
110	11108714	Selective ICE inhibition attenuates dsRNA + IFN-gamma-induced iNOS expression by primary beta-cells.
111	11108714	In addition, poly(I-C) + IFN-gamma-induced iNOS expression and nitric oxide production by human islets are prevented by interleukin-1 receptor antagonist protein, indicating that human islets respond to dsRNA and IFN-gamma in a manner similar to rat islets.
112	11108714	The viral replicative intermediate dsRNA stimulates beta-cell production of pro-IL-1beta, and following cleavage to its mature form by IFN-gamma-activated ICE, IL-1 then initiates beta-cell damage in a nitric oxide-dependent fashion.
113	11108714	In combination, synthetic dsRNA (polyinosinic-polycytidylic acid, poly(I-C)) and interferon (IFN)-gamma stimulate inducible nitric-oxide synthase (iNOS) expression, inhibit insulin secretion, and induce islet degeneration.
114	11108714	Interleukin-1 (IL-1) appears to mediate dsRNA + IFN-gamma-induced islet damage in a nitric oxide-dependent manner, as the interleukin-1 receptor antagonist protein prevents dsRNA + IFN-gamma-induced iNOS expression, inhibition of insulin secretion, and islet degeneration.
115	11108714	IL-1beta is synthesized as an inactive precursor protein that requires cleavage by the IL-1beta-converting enzyme (ICE) for activation. dsRNA and IFN-gamma stimulate IL-1beta expression and ICE activation in primary beta-cells, respectively.
116	11108714	Selective ICE inhibition attenuates dsRNA + IFN-gamma-induced iNOS expression by primary beta-cells.
117	11108714	In addition, poly(I-C) + IFN-gamma-induced iNOS expression and nitric oxide production by human islets are prevented by interleukin-1 receptor antagonist protein, indicating that human islets respond to dsRNA and IFN-gamma in a manner similar to rat islets.
118	11108714	The viral replicative intermediate dsRNA stimulates beta-cell production of pro-IL-1beta, and following cleavage to its mature form by IFN-gamma-activated ICE, IL-1 then initiates beta-cell damage in a nitric oxide-dependent fashion.
119	11108714	In combination, synthetic dsRNA (polyinosinic-polycytidylic acid, poly(I-C)) and interferon (IFN)-gamma stimulate inducible nitric-oxide synthase (iNOS) expression, inhibit insulin secretion, and induce islet degeneration.
120	11108714	Interleukin-1 (IL-1) appears to mediate dsRNA + IFN-gamma-induced islet damage in a nitric oxide-dependent manner, as the interleukin-1 receptor antagonist protein prevents dsRNA + IFN-gamma-induced iNOS expression, inhibition of insulin secretion, and islet degeneration.
121	11108714	IL-1beta is synthesized as an inactive precursor protein that requires cleavage by the IL-1beta-converting enzyme (ICE) for activation. dsRNA and IFN-gamma stimulate IL-1beta expression and ICE activation in primary beta-cells, respectively.
122	11108714	Selective ICE inhibition attenuates dsRNA + IFN-gamma-induced iNOS expression by primary beta-cells.
123	11108714	In addition, poly(I-C) + IFN-gamma-induced iNOS expression and nitric oxide production by human islets are prevented by interleukin-1 receptor antagonist protein, indicating that human islets respond to dsRNA and IFN-gamma in a manner similar to rat islets.
124	11108714	The viral replicative intermediate dsRNA stimulates beta-cell production of pro-IL-1beta, and following cleavage to its mature form by IFN-gamma-activated ICE, IL-1 then initiates beta-cell damage in a nitric oxide-dependent fashion.
125	11377701	Regulation of IL-18 production by IFN gamma and PGE2 in mouse microglial cells: involvement of NF-kB pathway in the regulatory processes.
126	11377701	Interleukin (IL)-18, a recently identified proinflammatory cytokine, has been implicated in a variety of pathological conditions such as rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory liver injury.
127	11377701	To understand how lymphokines and lipid mediators participate in the regulation of microglial IL-18 production, we assessed the effects of interferon (IFN)gamma, one of the major macrophage-activating lymphokines, and prostaglandin (PG)E(2), a lipid mediator produced in the brain, on IL-18 production and the expression of the IL-18 processing enzyme, caspase-1, in mouse microglial cells.
128	11377701	IFNgamma increased lipopolysaccharide (LPS)-induced IL-18 production and caspase-1 expression, while PGE(2) inhibited LPS-induced IL-18 production.
129	11377701	A similar pattern of IL-18 regulation by IFNgamma and PGE(2) was observed at the mRNA level.
130	11377701	The regulation of microglial activation by IFNgamma and PGE(2) was accompanied by differential modulation of LPS-induced NF-kB activation.
131	11377701	While IFNgamma enhanced LPS-induced NF-kB activation, PGE(2) suppressed its activation.
132	11377701	Regulation of IL-18 production by IFN gamma and PGE2 in mouse microglial cells: involvement of NF-kB pathway in the regulatory processes.
133	11377701	Interleukin (IL)-18, a recently identified proinflammatory cytokine, has been implicated in a variety of pathological conditions such as rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory liver injury.
134	11377701	To understand how lymphokines and lipid mediators participate in the regulation of microglial IL-18 production, we assessed the effects of interferon (IFN)gamma, one of the major macrophage-activating lymphokines, and prostaglandin (PG)E(2), a lipid mediator produced in the brain, on IL-18 production and the expression of the IL-18 processing enzyme, caspase-1, in mouse microglial cells.
135	11377701	IFNgamma increased lipopolysaccharide (LPS)-induced IL-18 production and caspase-1 expression, while PGE(2) inhibited LPS-induced IL-18 production.
136	11377701	A similar pattern of IL-18 regulation by IFNgamma and PGE(2) was observed at the mRNA level.
137	11377701	The regulation of microglial activation by IFNgamma and PGE(2) was accompanied by differential modulation of LPS-induced NF-kB activation.
138	11377701	While IFNgamma enhanced LPS-induced NF-kB activation, PGE(2) suppressed its activation.
139	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).
140	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.
141	14561487	The JNK binding domain of islet-brain 1 inhibits IL-1 induced JNK activity and apoptosis but not the transcription of key proapoptotic or protective genes in insulin-secreting cell lines.
142	14561487	The stress-activated protein kinase c-Jun NH2-terminal kinase (JNK) is a central signal for interleukin-1beta (IL-1beta)-induced apoptosis in insulin-producing beta-cells.
143	14561487	The cell-permeable peptide inhibitor of JNK (JNKI1), that introduces the JNK binding domain (JBD) of the scaffold protein islet-brain 1 (IB1) inside cells, effectively prevents beta-cell death caused by this cytokine.
144	14561487	To define the molecular targets of JNK involved in cytokine-induced beta-cell apoptosis we investigated whether JNKI1 or stable expression of JBD affected the expression of selected pro- and anti-apoptotic genes induced in rat (RIN-5AH-T2B) and mouse (betaTC3) insulinoma cells exposed to IL-1beta.
145	14561487	Inhibition of JNK significantly reduced phosphorylation of the specific JNK substrate c-Jun (p<0.05), IL-1beta-induced apoptosis (p<0.001), and IL-1beta-mediated c-fos gene expression.
146	14561487	However, neither JNKI1 nor JBD did influence IL-1beta-induced NO synthesis or iNOS expression or the transcription of the genes encoding mitochondrial manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase rho (GSTrho), heat shock protein (HSP) 70, IL-1beta-converting enzyme (ICE), caspase-3, apoptosis-inducing factor (AIF), Bcl-2 or Bcl-xL.
147	14592444	Tumor necrosis factor-alpha (TNF-alpha) is a cytokine considered to play a key role in beta-cell destruction in insulin-dependent diabetes mellitus (IDDM).
148	14592444	Expression of TNF receptor I, inducible form of nitric oxide synthase (iNOS), interleukin-1 beta-converting enzyme (ICE), Bcl-2, and nuclear factor kappa B (NF-kappa B) was analyzed by reverse transcriptase-polymerase chain reaction to investigate the suppressor mechanism of FTS on TNF-alpha-induced apoptosis.
149	14592444	FTS treatment suppressed the expression of iNOS and Bcl-2 mRNA in TNF-alpha-treated cells.
150	14592444	The expression of NF-kappa B mRNA in TNF-alpha-treated cells was enhanced after FTS treatment, while that of ICE mRNA did not change in TNF-alpha-treated cells with or without FTS treatment.
151	14592444	These results suggest that the inhibition of MIN6 cell death by FTS on TNF-alpha-induced apoptosis is caused by a negative feedback mechanism involving the inhibition of iNOS induction.
152	14592444	Tumor necrosis factor-alpha (TNF-alpha) is a cytokine considered to play a key role in beta-cell destruction in insulin-dependent diabetes mellitus (IDDM).
153	14592444	Expression of TNF receptor I, inducible form of nitric oxide synthase (iNOS), interleukin-1 beta-converting enzyme (ICE), Bcl-2, and nuclear factor kappa B (NF-kappa B) was analyzed by reverse transcriptase-polymerase chain reaction to investigate the suppressor mechanism of FTS on TNF-alpha-induced apoptosis.
154	14592444	FTS treatment suppressed the expression of iNOS and Bcl-2 mRNA in TNF-alpha-treated cells.
155	14592444	The expression of NF-kappa B mRNA in TNF-alpha-treated cells was enhanced after FTS treatment, while that of ICE mRNA did not change in TNF-alpha-treated cells with or without FTS treatment.
156	14592444	These results suggest that the inhibition of MIN6 cell death by FTS on TNF-alpha-induced apoptosis is caused by a negative feedback mechanism involving the inhibition of iNOS induction.
157	14693703	Interleukin (IL)-1 beta and IL-18 are two cytokines associated with the immunopathogenesis of diabetes in NOD mice.
158	14693703	IL-1 is a proinflammatory cytokine linked to beta-cell damage, and IL-18 stimulates production of interferon (IFN)gamma in synergy with IL-12.
159	14693703	Casp1(-/-) bone marrow-derived macrophages stimulated with lipopolysaccharide produced no detectable IL-18, fourfold lower IL-1 beta, and 20-30% less IL-1 alpha than macrophages from wild-type Casp1(+/+) or Casp1(+/-) controls.
160	14693703	Unexpectedly, despite reduced IL-1 and IL-18, there was no change in the rate of diabetes or in total incidence as compared with that in wild-type NOD mice.
161	14693703	These findings show that caspase-1 processing of IL-1 beta and IL-18 is not absolutely required for mediation of spontaneous or chemically induced diabetes pathogenesis in the NOD mouse.
162	14693703	Interleukin (IL)-1 beta and IL-18 are two cytokines associated with the immunopathogenesis of diabetes in NOD mice.
163	14693703	IL-1 is a proinflammatory cytokine linked to beta-cell damage, and IL-18 stimulates production of interferon (IFN)gamma in synergy with IL-12.
164	14693703	Casp1(-/-) bone marrow-derived macrophages stimulated with lipopolysaccharide produced no detectable IL-18, fourfold lower IL-1 beta, and 20-30% less IL-1 alpha than macrophages from wild-type Casp1(+/+) or Casp1(+/-) controls.
165	14693703	Unexpectedly, despite reduced IL-1 and IL-18, there was no change in the rate of diabetes or in total incidence as compared with that in wild-type NOD mice.
166	14693703	These findings show that caspase-1 processing of IL-1 beta and IL-18 is not absolutely required for mediation of spontaneous or chemically induced diabetes pathogenesis in the NOD mouse.
167	15013939	In addition, diabetes leads to the activation of caspase-1, the enzyme responsible for the production of the pro-inflammatory cytokines IL-1beta and IL-18 in the retinae of diabetic animals and diabetic patients.
168	17192486	We investigated the role of IL-1beta and caspase-1 (the enzyme that produces it) in diabetes-induced degeneration of retinal capillaries.
169	17192486	First, we investigated the effect of agents known to inhibit caspase-1 (minocycline and tetracycline) on IL-1beta production and retinal capillary degeneration in diabetic and galactose-fed mice.
170	17192486	At 2 months of diabetes, minocycline inhibited hyperglycemia-induced caspase-1 activity and IL-1beta production in the retina.
171	17192486	These results indicate that the caspase-1/IL-1beta signaling pathway plays an important role in diabetes-induced retinal pathology, and its inhibition might represent a new strategy to inhibit capillary degeneration in diabetic retinopathy.
172	17192486	We investigated the role of IL-1beta and caspase-1 (the enzyme that produces it) in diabetes-induced degeneration of retinal capillaries.
173	17192486	First, we investigated the effect of agents known to inhibit caspase-1 (minocycline and tetracycline) on IL-1beta production and retinal capillary degeneration in diabetic and galactose-fed mice.
174	17192486	At 2 months of diabetes, minocycline inhibited hyperglycemia-induced caspase-1 activity and IL-1beta production in the retina.
175	17192486	These results indicate that the caspase-1/IL-1beta signaling pathway plays an important role in diabetes-induced retinal pathology, and its inhibition might represent a new strategy to inhibit capillary degeneration in diabetic retinopathy.
176	17192486	We investigated the role of IL-1beta and caspase-1 (the enzyme that produces it) in diabetes-induced degeneration of retinal capillaries.
177	17192486	First, we investigated the effect of agents known to inhibit caspase-1 (minocycline and tetracycline) on IL-1beta production and retinal capillary degeneration in diabetic and galactose-fed mice.
178	17192486	At 2 months of diabetes, minocycline inhibited hyperglycemia-induced caspase-1 activity and IL-1beta production in the retina.
179	17192486	These results indicate that the caspase-1/IL-1beta signaling pathway plays an important role in diabetes-induced retinal pathology, and its inhibition might represent a new strategy to inhibit capillary degeneration in diabetic retinopathy.
180	17192486	We investigated the role of IL-1beta and caspase-1 (the enzyme that produces it) in diabetes-induced degeneration of retinal capillaries.
181	17192486	First, we investigated the effect of agents known to inhibit caspase-1 (minocycline and tetracycline) on IL-1beta production and retinal capillary degeneration in diabetic and galactose-fed mice.
182	17192486	At 2 months of diabetes, minocycline inhibited hyperglycemia-induced caspase-1 activity and IL-1beta production in the retina.
183	17192486	These results indicate that the caspase-1/IL-1beta signaling pathway plays an important role in diabetes-induced retinal pathology, and its inhibition might represent a new strategy to inhibit capillary degeneration in diabetic retinopathy.
184	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).
185	17267571	Diabetic mice had prolonged recovery from NSA that could be halved by administration of subcutaneous interleukin-1 (IL-1) receptor antagonist (RA).
186	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.
187	18263705	Glucose and leptin induce apoptosis in human beta-cells and impair glucose-stimulated insulin secretion through activation of c-Jun N-terminal kinases.
188	18263705	c-Jun N-terminal kinases (SAPK/JNKs) are activated by inflammatory cytokines, and JNK signaling is involved in insulin resistance and beta-cell secretory function and survival.
189	18263705	Chronic high glucose concentrations and leptin induce interleukin-1beta (IL-1beta) secretion from pancreatic islets, an event that is possibly causal in promoting beta-cell dysfunction and death.
190	18263705	The present study provides evidence that chronically elevated concentrations of leptin and glucose induce beta-cell apoptosis through activation of the JNK pathway in human islets and in insulinoma (INS 832/13) cells.
191	18263705	JNK inhibition by the dominant inhibitor JNK-binding domain of IB1/JIP-1 (JNKi) reduced JNK activity and apoptosis induced by leptin and glucose.
192	18263705	Exposure of human islets to leptin and high glucose concentrations leads to a decrease of glucose-induced insulin secretion, which was partly restored by JNKi.
193	18263705	We detected an interplay between the JNK cascade and the caspase 1/IL-1beta-converting enzyme in human islets.
194	18263705	Similarly, cultured human islets exposed to high glucose- and leptin-induced caspase 1 and JNK inhibition prevented this up-regulation.
195	18263705	Therefore, JNK inhibition may protect beta-cells from the deleterious effects of high glucose and leptin in diabetes.
196	18263705	Glucose and leptin induce apoptosis in human beta-cells and impair glucose-stimulated insulin secretion through activation of c-Jun N-terminal kinases.
197	18263705	c-Jun N-terminal kinases (SAPK/JNKs) are activated by inflammatory cytokines, and JNK signaling is involved in insulin resistance and beta-cell secretory function and survival.
198	18263705	Chronic high glucose concentrations and leptin induce interleukin-1beta (IL-1beta) secretion from pancreatic islets, an event that is possibly causal in promoting beta-cell dysfunction and death.
199	18263705	The present study provides evidence that chronically elevated concentrations of leptin and glucose induce beta-cell apoptosis through activation of the JNK pathway in human islets and in insulinoma (INS 832/13) cells.
200	18263705	JNK inhibition by the dominant inhibitor JNK-binding domain of IB1/JIP-1 (JNKi) reduced JNK activity and apoptosis induced by leptin and glucose.
201	18263705	Exposure of human islets to leptin and high glucose concentrations leads to a decrease of glucose-induced insulin secretion, which was partly restored by JNKi.
202	18263705	We detected an interplay between the JNK cascade and the caspase 1/IL-1beta-converting enzyme in human islets.
203	18263705	Similarly, cultured human islets exposed to high glucose- and leptin-induced caspase 1 and JNK inhibition prevented this up-regulation.
204	18263705	Therefore, JNK inhibition may protect beta-cells from the deleterious effects of high glucose and leptin in diabetes.
205	18274606	These changes include upregulation of iNOS, COX-2, ICAM-1, caspase 1, VEGF, and NF-kappaB, increased production of nitric oxide, prostaglandin E2, IL-1beta, and cytokines, as well as increased permeability and leukostasis.
206	19494813	T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes.
207	19494813	Here we show that mouse effector and memory CD4(+) T cells abolish macrophage inflammasome-mediated caspase-1 activation and subsequent interleukin 1beta release in a cognate manner.
208	19494813	Inflammasome inhibition is observed for all tested NLRP1 (commonly called NALP1) and NLRP3 (NALP3 or cryopyrin) activators, whereas NLRC4 (IPAF) inflammasome function and release of other inflammatory mediators such as CXCL2, interleukin 6 and tumour necrosis factor are not affected.
209	19494813	Suppression of the NLRP3 inflammasome requires cell-to-cell contact and can be mimicked by macrophage stimulation with selected ligands of the tumour necrosis factor family, such as CD40L (also known as CD40LG).
210	19494813	In a NLRP3-dependent peritonitis model, effector CD4(+) T cells are responsible for decreasing neutrophil recruitment in an antigen-dependent manner.
211	19805629	Inflammasomes activate caspase-1 for processing and secretion of the cytokines interleukin-1beta (IL-1beta) and IL-18.
212	19805629	Glyburide's cyclohexylurea group, which binds to adenosine triphosphatase (ATP)-sensitive K(+) (K(ATP)) channels for insulin secretion, is dispensable for inflammasome inhibition.
213	19805629	Glyburide analogues inhibit ATP- but not hypothermia-induced IL-1beta secretion from human monocytes expressing familial cold-associated autoinflammatory syndrome-associated Cryopyrin mutations, thus suggesting that inhibition occurs upstream of Cryopyrin.
214	19805629	Therefore, glyburide is the first identified compound to prevent Cryopyrin activation and microbial ligand-, DAMP-, and crystal-induced IL-1beta secretion.
215	20331890	IL-18 is found in the unstable atherosclerotic plaque, in adipose tissue and in muscle tissue, and is subject to several regulatory steps including cleavage by caspase-1, inactivation by IL-18 binding protein and the influence of other cytokines in modulating its interaction with the IL-18 receptor.
216	20370652	The ability of SIRT1 to avert apoptosis employs the activation of protein kinase B (Akt1), the post-translational phosphorylation of the forkhead member FoxO3a, the blocked trafficking of FoxO3a to the nucleus, and the inhibition of FoxO3a to initiate a "pro-apoptotic" program as shown by complimentary gene knockdown studies of FoxO3a.
217	20370652	Vascular apoptotic oversight by SIRT1 extends to the direct modulation of mitochondrial membrane permeability, cytochrome c release, Bad activation, and caspase 1 and 3 activation, since inhibition of SIRT1 activity and gene knockdown of SIRT1 significantly accentuate cascade progression while SIRT1 activation abrogates these apoptotic elements.
218	20370652	Our work identifies vascular SIRT1 and its control over early apoptotic membrane signaling, Akt1 activation, post-translational modification and trafficking of FoxO3a, mitochondrial permeability, Bad activation, and rapid caspase induction as new avenues for the treatment of vascular complications during DM.
219	21217695	The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance.
220	21217695	The Nod-like receptor (NLR) family of innate immune cell sensors, such as the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (Nlrp3, but also known as Nalp3 or cryopyrin) inflammasome are implicated in recognizing certain nonmicrobial originated 'danger signals' leading to caspase-1 activation and subsequent interleukin-1β (IL-1β) and IL-18 secretion.
221	21217695	We show that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity.
222	21217695	We further found that the Nlrp3 inflammasome senses lipotoxicity-associated increases in intracellular ceramide to induce caspase-1 cleavage in macrophages and adipose tissue.
223	21217695	Ablation of Nlrp3 in mice prevents obesity-induced inflammasome activation in fat depots and liver as well as enhances insulin signaling.
224	21217695	Furthermore, elimination of Nlrp3 in obese mice reduces IL-18 and adipose tissue interferon-γ (IFN-γ) expression, increases naive T cell numbers and reduces effector T cell numbers in adipose tissue.
225	21217695	Collectively, these data establish that the Nlrp3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.
226	21217695	The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance.
227	21217695	The Nod-like receptor (NLR) family of innate immune cell sensors, such as the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (Nlrp3, but also known as Nalp3 or cryopyrin) inflammasome are implicated in recognizing certain nonmicrobial originated 'danger signals' leading to caspase-1 activation and subsequent interleukin-1β (IL-1β) and IL-18 secretion.
228	21217695	We show that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity.
229	21217695	We further found that the Nlrp3 inflammasome senses lipotoxicity-associated increases in intracellular ceramide to induce caspase-1 cleavage in macrophages and adipose tissue.
230	21217695	Ablation of Nlrp3 in mice prevents obesity-induced inflammasome activation in fat depots and liver as well as enhances insulin signaling.
231	21217695	Furthermore, elimination of Nlrp3 in obese mice reduces IL-18 and adipose tissue interferon-γ (IFN-γ) expression, increases naive T cell numbers and reduces effector T cell numbers in adipose tissue.
232	21217695	Collectively, these data establish that the Nlrp3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.
233	21270263	Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1beta transcription in human adipose tissue.
234	21478880	Interleukin (IL)-1β plays a role in insulin resistance, yet how IL-1β is induced by the fatty acids in an HFD, and how this alters insulin signaling, is unclear.
235	21478880	We show that the saturated fatty acid palmitate, but not unsaturated oleate, induces the activation of the NLRP3-ASC inflammasome, causing caspase-1, IL-1β and IL-18 production.
236	21478880	This pathway involves mitochondrial reactive oxygen species and the AMP-activated protein kinase and unc-51-like kinase-1 (ULK1) autophagy signaling cascade.
237	21478880	Furthermore, IL-1β affects insulin sensitivity through tumor necrosis factor-independent and dependent pathways.
238	21523780	Limited proteolysis can take place extracellularly by serine proteases, released in particular by infiltrating neutrophils or intracellularly by the cysteine protease caspase-1.
239	21566058	As a new entry, the inflammasome-forming NLR genes integrate various danger signals into caspase-1-activating platforms that regulate the processing and secretion of pro-IL-1β and pro-IL-18 into the mature and active cytokines.
240	21566058	Accumulating data now document a role for the NLRP3 inflammasome and IL-1β/IL-18 in many diseases, including atherosclerosis, diabetes, amyloidosis, malaria, crystal-related diseases, and other autoinflammatory disorders, identifying this innate immune pathway as an attractive therapeutic target.
241	21566058	Here we review the current knowledge regarding inflammasome signaling and outline existing evidence on the expression and functional role of the inflammasome-caspase-1-IL-1β/IL-18 axis in kidney disease.
242	21566058	As a new entry, the inflammasome-forming NLR genes integrate various danger signals into caspase-1-activating platforms that regulate the processing and secretion of pro-IL-1β and pro-IL-18 into the mature and active cytokines.
243	21566058	Accumulating data now document a role for the NLRP3 inflammasome and IL-1β/IL-18 in many diseases, including atherosclerosis, diabetes, amyloidosis, malaria, crystal-related diseases, and other autoinflammatory disorders, identifying this innate immune pathway as an attractive therapeutic target.
244	21566058	Here we review the current knowledge regarding inflammasome signaling and outline existing evidence on the expression and functional role of the inflammasome-caspase-1-IL-1β/IL-18 axis in kidney disease.
245	22235789	We analyzed 14 single nucleotide polymorphisms (SNPs) within 7 inflammasome genes (NLRP1, NLRP3, NLRC4, AIM2, CARD8, CASP1, IL1B) in 144 patients affected by systemic lupus erythematosus and in 158 healthy controls from Southern Brazilian (state of São Paulo) with the aim of disclosing the possible role of inflammasome genes in the susceptibility of SLE.
246	22411934	NLRP3 activates inflammatory caspases, mostly caspase-1, which cleave the inactive precursors of IL-1β and IL-18 and stimulate their secretion.
247	22500248	Activation of these specific sets of receptors leads to the assembly of a multiprotein complex, the inflammasome, leading to the activation of caspase-1 and maturation of the cytokines interleukin (IL)-1β, IL-18, and IL-33.
248	22701621	In this study, we used streptozotocin (STZ)-induced diabetic nephropathy model with hyperuricemia and dyslipidemia in rats, and found over-expression of renal inflammasome components NLRP3, apoptosis-associated speck-like protein and Caspase-1, resulting in elevation of IL-1β and IL-18, with subsequently deteriorated renal injury.
249	23040364	It was subsequently observed that several of these conditions were caused by mutations in proteins involved in the innate immune response, including, among others, components of the NLRP3 inflammasome, cytokine receptors (tumour necrosis factor receptor 1 (TNFR1)) and receptor antagonists (interleukin 1 receptor antagonist (IL-1RA)).
250	23040364	NLRP3 inflammasome activation is induced by islet amyloid polypeptides (IAPPs) in T2D and this condition may, in future, be more commonly treated with targeted anti-cytokine therapies.
251	23040364	Caspase 1 activation and release of IL-1β/IL-1 family members is central to the pathogenesis of many autoinflammatory syndromes, as evidenced by the effectiveness of anti-IL-1 biologics in treating these disorders.
252	23066025	Multiple binding sites on the pyrin domain of ASC protein allow self-association and interaction with NLRP3 protein.
253	23066025	A key process underlying an innate immune response to pathogens or cellular stress is activation of members of the NOD-like receptor family, such as NLRP3, to assemble caspase-1-activating inflammasome complexes.
254	23066025	ASC interacts with NLRP3 via a homotypic PYD interaction and recruits procaspase-1 via a homotypic caspase recruitment domain interaction.
255	23066025	Here we demonstrate that ASC PYD contains two distinct binding sites important for self-association and interaction with NLRP3 and the modulatory protein POP1.
256	23066025	Furthermore, a type I binding mode is likely conserved in interactions with NLRP3 and POP1, because residues critical for interaction of ASC PYD are conserved in these PYDs.
257	23066025	We also demonstrate that ASC PYD can simultaneously self-associate and interact with NLRP3, rationalizing the model whereby ASC self-association upon recruitment to NLRP3 promotes clustering and activation of procaspase-1.
258	23086037	In this study, we investigated patterns of NLRP3 inflammasome activation in monocyte-derived macrophages (MDMs) from drug-naïve patients with newly diagnosed type 2 diabetes.
259	23086037	Type 2 diabetic subjects had significantly increased mRNA and protein expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and proinflammatory cytokines in MDMs cultured with autologous sera compared with healthy controls.
260	23086037	Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were observed in MDMs from type 2 diabetic patients after stimulation with various danger molecules (ATP, high-mobility group protein B1, free fatty acids, islet amyloid polypeptide, and monosodium uric acid crystals).
261	23086037	Mitochondrial reactive oxygen species and NLRP3 were required for IL-1β synthesis in MDMs.
262	23086037	Finally, 2 months of therapy with the antidiabetic drug metformin significantly inhibited the maturation of IL-1β in MDMs from patients with type 2 diabetes through AMP-activated protein kinase (AMPK) activation.
263	23103566	In the kidney, HFCS-55 enhanced the expression of the NLRP3 (nucleotide-binding domain and leucine-rich-repeat-protein 3) inflammasome complex, resulting in caspase-1 activation and interleukin-1β production.
264	23349493	We show that ablation of galectin-3 (Gal-3), a galactoside-binding lectin, accelerates high-fat diet-induced obesity and diabetes.
265	23349493	Obese LGALS3(-/-) mice have increased body weight, amount of total visceral adipose tissue (VAT), fasting blood glucose and insulin levels, homeostasis model assessment of insulin resistance, and markers of systemic inflammation compared with diet-matched wild-type (WT) animals.
266	23349493	VAT of obese LGALS3(-/-) mice exhibited increased incidence of type 1 T and NKT lymphocytes and proinflammatory CD11c(+)CD11b(+) macrophages and decreased CD4(+)CD25(+)FoxP3(+) regulatory T cells and M2 macrophages.
267	23349493	Pronounced mononuclear cell infiltrate, increased expression of NLRP3 inflammasome and interleukin-1β (IL-1β) in macrophages, and increased accumulation of advanced glycation end products (AGEs) and receptor for AGE (RAGE) expression were present in pancreatic islets of obese LGALS3(-/-) animals accompanied with elevated phosphorylated nuclear factor-κB (NF-κB) p65 and mature caspase-1 protein expression in pancreatic tissue and VAT.
268	23349493	In vitro stimulation of LGALS3(-/-) peritoneal macrophages with lipopolysaccharide (LPS) and saturated fatty acid palmitate caused increased caspase-1-dependent IL-1β production and increased phosphorylation of NF-κB p65 compared with WT cells.
269	23349493	Transfection of LGALS3(-/-) macrophages with NLRP3 small interfering RNA attenuated IL-1β production in response to palmitate and LPS plus palmitate.
270	23349493	We show that ablation of galectin-3 (Gal-3), a galactoside-binding lectin, accelerates high-fat diet-induced obesity and diabetes.
271	23349493	Obese LGALS3(-/-) mice have increased body weight, amount of total visceral adipose tissue (VAT), fasting blood glucose and insulin levels, homeostasis model assessment of insulin resistance, and markers of systemic inflammation compared with diet-matched wild-type (WT) animals.
272	23349493	VAT of obese LGALS3(-/-) mice exhibited increased incidence of type 1 T and NKT lymphocytes and proinflammatory CD11c(+)CD11b(+) macrophages and decreased CD4(+)CD25(+)FoxP3(+) regulatory T cells and M2 macrophages.
273	23349493	Pronounced mononuclear cell infiltrate, increased expression of NLRP3 inflammasome and interleukin-1β (IL-1β) in macrophages, and increased accumulation of advanced glycation end products (AGEs) and receptor for AGE (RAGE) expression were present in pancreatic islets of obese LGALS3(-/-) animals accompanied with elevated phosphorylated nuclear factor-κB (NF-κB) p65 and mature caspase-1 protein expression in pancreatic tissue and VAT.
274	23349493	In vitro stimulation of LGALS3(-/-) peritoneal macrophages with lipopolysaccharide (LPS) and saturated fatty acid palmitate caused increased caspase-1-dependent IL-1β production and increased phosphorylation of NF-κB p65 compared with WT cells.
275	23349493	Transfection of LGALS3(-/-) macrophages with NLRP3 small interfering RNA attenuated IL-1β production in response to palmitate and LPS plus palmitate.
276	23382179	Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a key regulator of the innate immune system, particularly in the skin where, in response to molecular triggers such as pathogen-associated or damage-associated molecular patterns, the NLRP1 inflammasome promotes caspase-1-dependent processing of bioactive interleukin-1β (IL-1β), resulting in IL-1β secretion and downstream inflammatory responses.
277	23382179	Functionally, we found that peripheral blood monocytes from healthy subjects homozygous for the predominant high-risk haplotype 2A processed significantly greater (P < 0.0001) amounts of the IL-1β precursor to mature bioactive IL-1β under basal (resting) conditions and in response to Toll-like receptor (TLR) agonists (TLR2 and TLR4) compared with monocytes from subjects homozygous for the reference haplotype 1.
278	23434541	Extracellular ATP can cause P2X receptors to activate the NOD-like receptor 3 (NLRP3) inflammasome and cause IL-1β and IL-18 maturation and release.
279	23434541	Linear correlation analysis shows that P2X4 expression was positively related with urine IL-1β and IL-18 levels.
280	23434541	Moreover, P2X4 expression was co-localized with NLRP3, IL-1β, and IL-18 expression.
281	23434541	In vitro culture experiments showed NLRP3 protein expression, cleavage of caspase-1 and IL-1β, and release of IL-1β, IL-18 and ATP in HK-2 cells significantly increased after high glucose stimulation.
282	23434541	The P2 receptor antagonist suramin, P2X receptor antagonist TNP-ATP, P2X4 selective antagonist 5-BDBD, and P2X4 gene silencing attenuated NLRP3 expression, cleavage of caspase-1 and IL-1β, and release of IL-1β and IL-18 induced by high glucose.
283	23434541	Taken together, these results suggest that ATP-P2X4 signaling mediates high glucose-induced activation of the NLRP3 inflammasome, regulates IL-1 family cytokine secretion, and causes the development of tubulointerstitial inflammation in DN.
284	23434541	Extracellular ATP can cause P2X receptors to activate the NOD-like receptor 3 (NLRP3) inflammasome and cause IL-1β and IL-18 maturation and release.
285	23434541	Linear correlation analysis shows that P2X4 expression was positively related with urine IL-1β and IL-18 levels.
286	23434541	Moreover, P2X4 expression was co-localized with NLRP3, IL-1β, and IL-18 expression.
287	23434541	In vitro culture experiments showed NLRP3 protein expression, cleavage of caspase-1 and IL-1β, and release of IL-1β, IL-18 and ATP in HK-2 cells significantly increased after high glucose stimulation.
288	23434541	The P2 receptor antagonist suramin, P2X receptor antagonist TNP-ATP, P2X4 selective antagonist 5-BDBD, and P2X4 gene silencing attenuated NLRP3 expression, cleavage of caspase-1 and IL-1β, and release of IL-1β and IL-18 induced by high glucose.
289	23434541	Taken together, these results suggest that ATP-P2X4 signaling mediates high glucose-induced activation of the NLRP3 inflammasome, regulates IL-1 family cytokine secretion, and causes the development of tubulointerstitial inflammation in DN.
290	23689355	Caspase-1 is a member of the intracellular cysteine protease family that mediates inflammation through the activation of the cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18).
291	23689355	As mice lacking IL-18 become obese and insulin resistant, and both IL-18 and IL-1β have a role in overall energy balance, we sought to determine whether caspase-1 deficiency also causes obesity.
292	23689355	Caspase-1-/- mice maintained lower but detectable levels of IL-18 compared with WT mice.
293	23689355	Overall, this study suggests that the lower level of IL-18 in caspase-1-/- mice might be causing obesity development similarly to IL-18-deficient mice.
294	23689355	Caspase-1 is a member of the intracellular cysteine protease family that mediates inflammation through the activation of the cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18).
295	23689355	As mice lacking IL-18 become obese and insulin resistant, and both IL-18 and IL-1β have a role in overall energy balance, we sought to determine whether caspase-1 deficiency also causes obesity.
296	23689355	Caspase-1-/- mice maintained lower but detectable levels of IL-18 compared with WT mice.
297	23689355	Overall, this study suggests that the lower level of IL-18 in caspase-1-/- mice might be causing obesity development similarly to IL-18-deficient mice.
298	23689355	Caspase-1 is a member of the intracellular cysteine protease family that mediates inflammation through the activation of the cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18).
299	23689355	As mice lacking IL-18 become obese and insulin resistant, and both IL-18 and IL-1β have a role in overall energy balance, we sought to determine whether caspase-1 deficiency also causes obesity.
300	23689355	Caspase-1-/- mice maintained lower but detectable levels of IL-18 compared with WT mice.
301	23689355	Overall, this study suggests that the lower level of IL-18 in caspase-1-/- mice might be causing obesity development similarly to IL-18-deficient mice.
302	23689355	Caspase-1 is a member of the intracellular cysteine protease family that mediates inflammation through the activation of the cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18).
303	23689355	As mice lacking IL-18 become obese and insulin resistant, and both IL-18 and IL-1β have a role in overall energy balance, we sought to determine whether caspase-1 deficiency also causes obesity.
304	23689355	Caspase-1-/- mice maintained lower but detectable levels of IL-18 compared with WT mice.
305	23689355	Overall, this study suggests that the lower level of IL-18 in caspase-1-/- mice might be causing obesity development similarly to IL-18-deficient mice.
306	23762057	The levels of IL-1β, IL-6, IL-15, and TNF-α were found to be decreased in T2DM patients, whereas the levels of IL-10, IFN-γ, and caspase-1 were increased, compared to normal controls.
307	23762057	T2DM patients with hypertension show significantly decreased levels of IL-1β and caspase-1 compared to patients without hypertension.
308	23762057	Significant correlations were found between HbA1c and IL-6; body mass index (BMI) was significantly correlated with CRP, TNF-α, and phosphate; the weight (Wt) was associated with CRP and IFN-γ.
309	23762057	The levels of IL-1β, IL-6, IL-15, and TNF-α were found to be decreased in T2DM patients, whereas the levels of IL-10, IFN-γ, and caspase-1 were increased, compared to normal controls.
310	23762057	T2DM patients with hypertension show significantly decreased levels of IL-1β and caspase-1 compared to patients without hypertension.
311	23762057	Significant correlations were found between HbA1c and IL-6; body mass index (BMI) was significantly correlated with CRP, TNF-α, and phosphate; the weight (Wt) was associated with CRP and IFN-γ.
312	23809162	Here we show that stimulation of macrophages with ω-3 FAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and other family members, abolished NLRP3 inflammasome activation and inhibited subsequent caspase-1 activation and IL-1β secretion.
313	23823918	The expression levels of genes that cause IL-18 activation (IL-18, IL-18 receptor and caspase-1) in OLETF rats were increased at 60 weeks of age, and the levels of IL-18 and IFN-γ in 60-week-old OLETF rat retinas were also higher than in 60-week-old LETO rats.
314	23836106	RT-PCR showed NLRP3 inflammasome activation in the fat pads of both leptin-deficient and high-fat diet obese mice, in which formation of active caspase-1 was documented by immunohistochemistry in the cytoplasm of several hypertrophic adipocytes.
315	23836106	NLRP3-dependent caspase-1 activation in hypertrophic adipocytes likely induces obese adipocyte death by pyroptosis, a proinflammatory programmed cell death.
316	23836106	RT-PCR showed NLRP3 inflammasome activation in the fat pads of both leptin-deficient and high-fat diet obese mice, in which formation of active caspase-1 was documented by immunohistochemistry in the cytoplasm of several hypertrophic adipocytes.
317	23836106	NLRP3-dependent caspase-1 activation in hypertrophic adipocytes likely induces obese adipocyte death by pyroptosis, a proinflammatory programmed cell death.
318	23852602	Pathogen-stimulated NLRs such as NLR family Pyrin domain-containing protein 1 (NLRP1) assemble into molecular platforms called "inflammasomes" to activate inflammatory protease caspase-1, which processes pro-IL-1β and pro-IL-18 into active cytokines.
319	23852602	Protocols are provided for: (a) expression and purification of inflammasome core components (NLRP1 and pro-caspase-1 proteins) using the baculovirus/insect cell expression system, and (b) functional monitoring of NLRP1-mediated caspase-1 activation in response to NLRP1 ligand muramyl dipeptide (MDP) and ATP.
320	23852602	Pathogen-stimulated NLRs such as NLR family Pyrin domain-containing protein 1 (NLRP1) assemble into molecular platforms called "inflammasomes" to activate inflammatory protease caspase-1, which processes pro-IL-1β and pro-IL-18 into active cytokines.
321	23852602	Protocols are provided for: (a) expression and purification of inflammasome core components (NLRP1 and pro-caspase-1 proteins) using the baculovirus/insect cell expression system, and (b) functional monitoring of NLRP1-mediated caspase-1 activation in response to NLRP1 ligand muramyl dipeptide (MDP) and ATP.
322	24006511	Palmitate and stearate, both SFAs, triggered IL-1β secretion in a caspase-1/ASC/NLRP3-dependent pathway.
323	24014157	Inflammasome is a multiprotein complex consisting of Nod-like receptor proteins (NLRPs), apoptosis-associated speck-like protein (ASC), and caspase 1 or 5, which functions to switch on the inflammatory process and the release of inflammatory factors.
324	24014157	The results demonstrated that the levels of interleukin-1 beta (IL-1β) were increased in the cortex of streptozocin (STZ)-induced diabetic rats.
325	24014157	The levels of mature IL-1β and IL-18 were also elevated in culture medium of neurons treated with high glucose (50 mM).
326	24014157	The expression of three essential components of the NLRP1 inflammasome complex, namely, NLRP1, ASC, and caspase 1, was also upregulated in vivo and in vitro under high glucose.
327	24014157	Silencing the ASC gene prevented the caspase-1 activation, and inhibiting caspase 1 activity blocked hyperglycemia-induced release of inflammatory factors and neuron injury.
328	24014157	Inflammasome is a multiprotein complex consisting of Nod-like receptor proteins (NLRPs), apoptosis-associated speck-like protein (ASC), and caspase 1 or 5, which functions to switch on the inflammatory process and the release of inflammatory factors.
329	24014157	The results demonstrated that the levels of interleukin-1 beta (IL-1β) were increased in the cortex of streptozocin (STZ)-induced diabetic rats.
330	24014157	The levels of mature IL-1β and IL-18 were also elevated in culture medium of neurons treated with high glucose (50 mM).
331	24014157	The expression of three essential components of the NLRP1 inflammasome complex, namely, NLRP1, ASC, and caspase 1, was also upregulated in vivo and in vitro under high glucose.
332	24014157	Silencing the ASC gene prevented the caspase-1 activation, and inhibiting caspase 1 activity blocked hyperglycemia-induced release of inflammatory factors and neuron injury.
333	24014157	Inflammasome is a multiprotein complex consisting of Nod-like receptor proteins (NLRPs), apoptosis-associated speck-like protein (ASC), and caspase 1 or 5, which functions to switch on the inflammatory process and the release of inflammatory factors.
334	24014157	The results demonstrated that the levels of interleukin-1 beta (IL-1β) were increased in the cortex of streptozocin (STZ)-induced diabetic rats.
335	24014157	The levels of mature IL-1β and IL-18 were also elevated in culture medium of neurons treated with high glucose (50 mM).
336	24014157	The expression of three essential components of the NLRP1 inflammasome complex, namely, NLRP1, ASC, and caspase 1, was also upregulated in vivo and in vitro under high glucose.
337	24014157	Silencing the ASC gene prevented the caspase-1 activation, and inhibiting caspase 1 activity blocked hyperglycemia-induced release of inflammatory factors and neuron injury.