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	AIM2	1 hits
2	BCL2	1 hits
3	BIRC3	1 hits
4	CARD9	1 hits
5	CASP2	1 hits
6	CASP8	1 hits
7	CD4	1 hits
8	CTSB	1 hits
9	FAS	1 hits
10	FASLG	1 hits
11	GZMB	1 hits
12	IL12A	1 hits
13	IL17A	1 hits
14	IL18	1 hits
15	IL1A	1 hits
16	IL1B	1 hits
17	IL1RAPL2	1 hits
18	IL23A	1 hits
19	IL33	1 hits
20	IL4	1 hits
21	IL5	1 hits
22	IL6	1 hits
23	KRR1	1 hits
24	MAPK14	1 hits
25	MYD88	1 hits
26	NAIP	1 hits
27	NLRC4	1 hits
28	NLRP1	1 hits
29	NLRP3	1 hits
30	PRKAR1A	1 hits
31	PRKAR2A	1 hits
32	PSAP	1 hits
33	PYCARD	1 hits
34	RIPK1	1 hits
35	RIPK3	1 hits
36	RNASEL	1 hits
37	TERT	1 hits
38	TICAM1	1 hits
39	TLR2	1 hits
40	TLR5	1 hits
41	TLR8	1 hits
42	TNF	1 hits
43	TNFRSF25	1 hits
44	VWS	1 hits

Related Sentences

#	PMID	Sentence
1	7830531	Vaccination with streptococcal extracellular cysteine protease (interleukin-1 beta convertase) protects mice against challenge with heterologous group A streptococci.
2	7830531	Virtually all clinical isolates of group A streptococci secrete a highly conserved extracellular cysteine protease that cleaves human fibronectin and vitronectin, and converts IL-1 beta precursor to biologically active IL-1 beta.
3	10525448	Interleukin (IL)-18 is a newly discovered cytokine, structurally similar to IL-1, with profound effects on T-cell activation.
4	10525448	Formerly called interferon (IFN) gamma inducing factor (IGIF), IL-18 is the new name of a novel cytokine that plays an important role in the T-cell-helper type 1 (Th1) response, primarily by its ability to induce IFNgamma production in T cells and natural killer (NK) cells.
5	10525448	Mice deficient in IL-18 have suppressed IFNgamma production despite the presence of IL-12 IL-18 is related to the IL-1 family in terms of structure, receptor family, and function.
6	10525448	In terms of structure, IL-18 and IL-1beta share primary amino acid sequences of the so-called "signature sequence" motif and are similarly folded as all-beta pleated sheet molecules.
7	10525448	Also similar to IL-1beta, IL-18 is synthesized as a biologically inactive precursor molecule lacking a signal peptide which requires cleavage into an active, mature molecule by the intracellular cysteine protease called IL-1beta-converting enzyme (ICE, also called caspase-1).
8	10525448	The activity of mature IL-18 is closely related to that of IL-1.
9	10525448	IL-18 induces gene expression and synthesis of tumor necrosis factor (TNF), IL-1, Fas ligand, and several chemokines.
10	10525448	This IL-18R complex is made up of a binding chain termed IL-18Ralpha, a member of the IL-1 receptor family previously identified as the IL-1 receptor-related protein (IL-1Rrp), and a signaling chain, also a member of the IL-1R family.
11	10525448	The IL-18R complex recruits the IL-1R-activating kinase (IRAK) and TNFR-associated factor-6 (TRAF-6) which phosphorylates nuclear factor kappaB (NFkappaB)-inducing kinase (NIK) with subsequent activation of NFkappaB.
12	10525448	Thus on the basis of primary structure, three-dimensional structure, receptor family, signal transduction pathways and biological effects, IL-18 appears to be a new member of the IL-1 family.
13	10525448	Similar to IL-1, IL-18 participates in both innate and acquired immunity.
14	11007365	The molecular machinery at the nexus of apoptosis and inflammation includes caspase-1 --an activator of IL-1beta and IL-18 - as well as the double-stranded-RNA-dependent protein kinase pathway and RNaseL pathway, which are key effectors of antiviral immunity.
15	12620640	These Pw-induced changes were accompanied by an increase in caspase-1 and interleukin-1beta (IL-1beta), and were associated with increased activity of the stress-activated kinase, p38.
16	12620640	In contrast, immunization with Pa failed to activate pro-inflammatory IL-1 responses but resulted in increased IL-1 receptor antagonist (IL-1ra) production.
17	12874344	Moreover, activation of caspase 9 and the executioner caspase 3 was also observed in the LVS-infected J774A.1 macrophages.
18	12874344	The activated caspase 3 degraded poly(ADP-ribose) polymerase (PARP).
19	12874344	The internucleosomal fragmentation and PARP degradation resulting from activation of this apoptotic pathway was prevented by the caspase 3 inhibitor Z-DEVD-fmk.
20	12874344	No involvement of caspase 1, caspase 8, Bcl-2, or Bid was observed.
21	12887180	Candidate gene approach: potentional association of caspase-1, inhibitor of apoptosis protein-1, and prosaposin gene polymorphisms with response to Salmonella enteritidis challenge or vaccination in young chicks.
22	12887180	Caspase-1 and inhibitor of apoptosis protein-1 (IAP-1) were selected as candidate genes for chicken response to SE because their proteins play critical roles in the apoptotic pathway when intracellular bacteria interact with host cells.
23	12887180	This study is the first to demonstrate the association of SNPs for caspase-1, IAP-1, and PSAP genes with SE vaccine and with pathogen challenge response in chickens.
24	12887180	Candidate gene approach: potentional association of caspase-1, inhibitor of apoptosis protein-1, and prosaposin gene polymorphisms with response to Salmonella enteritidis challenge or vaccination in young chicks.
25	12887180	Caspase-1 and inhibitor of apoptosis protein-1 (IAP-1) were selected as candidate genes for chicken response to SE because their proteins play critical roles in the apoptotic pathway when intracellular bacteria interact with host cells.
26	12887180	This study is the first to demonstrate the association of SNPs for caspase-1, IAP-1, and PSAP genes with SE vaccine and with pathogen challenge response in chickens.
27	12887180	Candidate gene approach: potentional association of caspase-1, inhibitor of apoptosis protein-1, and prosaposin gene polymorphisms with response to Salmonella enteritidis challenge or vaccination in young chicks.
28	12887180	Caspase-1 and inhibitor of apoptosis protein-1 (IAP-1) were selected as candidate genes for chicken response to SE because their proteins play critical roles in the apoptotic pathway when intracellular bacteria interact with host cells.
29	12887180	This study is the first to demonstrate the association of SNPs for caspase-1, IAP-1, and PSAP genes with SE vaccine and with pathogen challenge response in chickens.
30	15899823	Administration of gamma-irradiated TRAMP-C2 cells preinfected with adenovirus containing both B7-1 and IL-12 genes, unlike adenovirus containing B7-1 alone, considerably protected C57BL/6 mice from TRAMP-C2 tumor growth and extended the life span of TRAMP mice.
31	15899823	Whereas injections of ligand-inducible caspase-1- and IL-12-containing adenoviruses cured small s.c.
32	15899823	The antitumor immune responses involved CD4+-, CD8+-, and natural killer cells and were strengthened by increasing the number of vaccinations.
33	15899823	Intraprostatic administration of inducible caspase-1- and IL-12-containing adenoviruses resulted in local cell death and improved survival of adenocarcinoma-bearing TRAMP mice.
34	15899823	Administration of gamma-irradiated TRAMP-C2 cells preinfected with adenovirus containing both B7-1 and IL-12 genes, unlike adenovirus containing B7-1 alone, considerably protected C57BL/6 mice from TRAMP-C2 tumor growth and extended the life span of TRAMP mice.
35	15899823	Whereas injections of ligand-inducible caspase-1- and IL-12-containing adenoviruses cured small s.c.
36	15899823	The antitumor immune responses involved CD4+-, CD8+-, and natural killer cells and were strengthened by increasing the number of vaccinations.
37	15899823	Intraprostatic administration of inducible caspase-1- and IL-12-containing adenoviruses resulted in local cell death and improved survival of adenocarcinoma-bearing TRAMP mice.
38	16895974	Using cells derived from TLR2-deficient mice and in vitro transfection assays, we demonstrated that this response was mediated by TLR2 and did not require the LPS-binding protein.
39	16895974	F. tularensis appeared to activate TLR2/TLR1 and TLR2/TLR6 heterodimers.
40	16895974	IL-1beta secretion, a reflection of caspase-1 activation, was induced by live but not heat-killed F. tularensis, despite the fact that both forms of the bacterium equally induced the IL-1beta transcript.
41	17485153	Both aluminum-containing adjuvants significantly increased the expression of CD86 on DCs but only aluminum hydroxide adjuvant also induced moderate expression of CD80.
42	17485153	Aluminum-containing adjuvants stimulated the release of IL-1beta and IL-18 from DCs via caspase-1 activation.
43	17485153	In contrast, DCs incubated with aluminum/OVA activated CD4(+) T cells to secrete IL-4 and IL-5 as well as IFN-gamma.
44	17485153	Addition of neutralizing anti-IL-1beta antibodies decreased IL-5 production and addition of anti-IL-18 antibodies decreased both IL-4 and IL-5 production.
45	17485153	Inhibition of IL-1beta and IL-18 secretion by DCs via inhibition of caspase-1 also led to a marked decrease of IL-4 and IL-5 by CD4(+) T cells.
46	17485153	These results indicate that aluminum-containing adjuvants activate DCs and influence their ability to direct T(H)1 and T(H)2 responses through the secretion of IL-1beta and IL-18.
47	17485153	Both aluminum-containing adjuvants significantly increased the expression of CD86 on DCs but only aluminum hydroxide adjuvant also induced moderate expression of CD80.
48	17485153	Aluminum-containing adjuvants stimulated the release of IL-1beta and IL-18 from DCs via caspase-1 activation.
49	17485153	In contrast, DCs incubated with aluminum/OVA activated CD4(+) T cells to secrete IL-4 and IL-5 as well as IFN-gamma.
50	17485153	Addition of neutralizing anti-IL-1beta antibodies decreased IL-5 production and addition of anti-IL-18 antibodies decreased both IL-4 and IL-5 production.
51	17485153	Inhibition of IL-1beta and IL-18 secretion by DCs via inhibition of caspase-1 also led to a marked decrease of IL-4 and IL-5 by CD4(+) T cells.
52	17485153	These results indicate that aluminum-containing adjuvants activate DCs and influence their ability to direct T(H)1 and T(H)2 responses through the secretion of IL-1beta and IL-18.
53	17495947	Interleukin-18 (IL-18) is an essential cytokine for the generation of Th1 response and natural killer cells and cytotoxic T lymphocytes (CTL) activation.
54	17495947	As MBD2 and IL-18 appear to function on different components required by an effective antitumor immune response including both innate and adaptive immunity, we investigated whether combinatorial delivery of MBD2 and IL-18 transduced L1210 cells could elicit synergistic antileukemia effects.
55	17495947	First, we constructed a single plasmid vector carrying both pro-IL-18 and IL-1beta converting enzyme (ICE) genes, and found that transfection of this vector into L1210 cells resulted in efficient secretion of bioactive IL-18.
56	17495947	These results suggest that the combination of MBD2 and IL-18 induces more effective antileukemia activity and provides a promising strategy for cancer therapy.
57	18453609	The observation that intracellular Ft LVS colocalizes with TLR2 and MyD88 inside macrophages suggested that Ft LVS might signal from within the phagosome.
58	18453609	IL-1beta secretion was also diminished in Ft LVS-infected IFN-beta(-/-) macrophages. rIFN-beta failed to restore IL-1beta secretion in LVSDeltaiglC-infected macrophages, suggesting that signals in addition to IFN-beta are required for assembly of the inflammasome and activation of caspase-1.
59	18493980	Previous reports suggested that lethal toxin (LT)-induced caspase-1 activity and/or IL-1beta accounted for Bacillus anthracis (BA) infection lethality.
60	18493980	In contrast, we now report that caspase-1-mediated IL-1beta expression in response to BA spores is required for anti-BA host defenses.
61	18493980	Caspase-1(-/-) and IL-1beta(-/-) mice are more susceptible than wild-type (WT) mice to lethal BA infection, are less able to kill BA both in vivo and in vitro, and addition of rIL-1beta to macrophages from these mice restored killing in vitro.
62	18493980	Non-germinating BA spores induced caspase-1 activity, IL-1beta and nitric oxide, by which BA are killed in WT but not in caspase-1(-/-) mice, suggesting that the spore itself stimulated inflammatory responses.
63	18493980	While both spores and LT induced caspase-1 activity and IL-1beta, LT did not induce IL-1beta mRNA, and spores did not induce cell death.
64	18493980	Previous reports suggested that lethal toxin (LT)-induced caspase-1 activity and/or IL-1beta accounted for Bacillus anthracis (BA) infection lethality.
65	18493980	In contrast, we now report that caspase-1-mediated IL-1beta expression in response to BA spores is required for anti-BA host defenses.
66	18493980	Caspase-1(-/-) and IL-1beta(-/-) mice are more susceptible than wild-type (WT) mice to lethal BA infection, are less able to kill BA both in vivo and in vitro, and addition of rIL-1beta to macrophages from these mice restored killing in vitro.
67	18493980	Non-germinating BA spores induced caspase-1 activity, IL-1beta and nitric oxide, by which BA are killed in WT but not in caspase-1(-/-) mice, suggesting that the spore itself stimulated inflammatory responses.
68	18493980	While both spores and LT induced caspase-1 activity and IL-1beta, LT did not induce IL-1beta mRNA, and spores did not induce cell death.
69	18493980	Previous reports suggested that lethal toxin (LT)-induced caspase-1 activity and/or IL-1beta accounted for Bacillus anthracis (BA) infection lethality.
70	18493980	In contrast, we now report that caspase-1-mediated IL-1beta expression in response to BA spores is required for anti-BA host defenses.
71	18493980	Caspase-1(-/-) and IL-1beta(-/-) mice are more susceptible than wild-type (WT) mice to lethal BA infection, are less able to kill BA both in vivo and in vitro, and addition of rIL-1beta to macrophages from these mice restored killing in vitro.
72	18493980	Non-germinating BA spores induced caspase-1 activity, IL-1beta and nitric oxide, by which BA are killed in WT but not in caspase-1(-/-) mice, suggesting that the spore itself stimulated inflammatory responses.
73	18493980	While both spores and LT induced caspase-1 activity and IL-1beta, LT did not induce IL-1beta mRNA, and spores did not induce cell death.
74	18493980	Previous reports suggested that lethal toxin (LT)-induced caspase-1 activity and/or IL-1beta accounted for Bacillus anthracis (BA) infection lethality.
75	18493980	In contrast, we now report that caspase-1-mediated IL-1beta expression in response to BA spores is required for anti-BA host defenses.
76	18493980	Caspase-1(-/-) and IL-1beta(-/-) mice are more susceptible than wild-type (WT) mice to lethal BA infection, are less able to kill BA both in vivo and in vitro, and addition of rIL-1beta to macrophages from these mice restored killing in vitro.
77	18493980	Non-germinating BA spores induced caspase-1 activity, IL-1beta and nitric oxide, by which BA are killed in WT but not in caspase-1(-/-) mice, suggesting that the spore itself stimulated inflammatory responses.
78	18493980	While both spores and LT induced caspase-1 activity and IL-1beta, LT did not induce IL-1beta mRNA, and spores did not induce cell death.
79	18493980	Previous reports suggested that lethal toxin (LT)-induced caspase-1 activity and/or IL-1beta accounted for Bacillus anthracis (BA) infection lethality.
80	18493980	In contrast, we now report that caspase-1-mediated IL-1beta expression in response to BA spores is required for anti-BA host defenses.
81	18493980	Caspase-1(-/-) and IL-1beta(-/-) mice are more susceptible than wild-type (WT) mice to lethal BA infection, are less able to kill BA both in vivo and in vitro, and addition of rIL-1beta to macrophages from these mice restored killing in vitro.
82	18493980	Non-germinating BA spores induced caspase-1 activity, IL-1beta and nitric oxide, by which BA are killed in WT but not in caspase-1(-/-) mice, suggesting that the spore itself stimulated inflammatory responses.
83	18493980	While both spores and LT induced caspase-1 activity and IL-1beta, LT did not induce IL-1beta mRNA, and spores did not induce cell death.
84	18496530	Furthermore, in vivo, mice deficient in Nalp3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) or caspase-1 failed to mount a significant antibody response to an antigen administered with aluminium adjuvants, whereas the response to complete Freund's adjuvant remained intact.
85	18566365	We have recently shown that alum activates caspase-1 and induces secretion of mature IL-1beta and IL-18.
86	18566365	In this study we show that, in human and mouse macrophages, alum-induced secretion of IL-1beta, IL-18, and IL-33 is mediated by the NLR (nucleotide-binding domain leucine-rich repeat-containing) protein NLRP3 and its adaptor ASC, but not by NLRC4.
87	18624356	The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity.
88	18624356	Alum has recently been shown to promote caspase-1 activation and IL-1beta secretion, but the cellular pathways involved remain elusive.
89	18624356	Here we report that the release of IL-1beta triggered by alum is abrogated in macrophages deficient in the NLR family, pyrin domain containing 3 (Nlrp3) protein and the apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) but not the NLR family, CARD domain containing 4 (Nlrc4) protein.
90	18624356	The requirement of the Nlrp3 inflammasome was specific for IL-1beta in that secretion of TNF-alpha was independent of Nlrp3 or Asc.
91	18624356	Consistently, processing of pro-caspase-1 induced by alum was abolished in macrophages lacking Nlrp3 or Asc.
92	18624356	Unlike caspase-1 processing and IL-1beta secretion triggered by LPS, alum-mediated activation of the inflammasome did not require exogenous ATP.
93	18624356	Importantly, induction of IgG production against human serum albumin by alum was unimpaired in mice deficient in Nlrp3.
94	18624356	These results indicate that alum induces IL-1beta via the Nlrp3 inflammasome but this activity is dispensable for alum-mediated adjuvant activity.
95	18624356	The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity.
96	18624356	Alum has recently been shown to promote caspase-1 activation and IL-1beta secretion, but the cellular pathways involved remain elusive.
97	18624356	Here we report that the release of IL-1beta triggered by alum is abrogated in macrophages deficient in the NLR family, pyrin domain containing 3 (Nlrp3) protein and the apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) but not the NLR family, CARD domain containing 4 (Nlrc4) protein.
98	18624356	The requirement of the Nlrp3 inflammasome was specific for IL-1beta in that secretion of TNF-alpha was independent of Nlrp3 or Asc.
99	18624356	Consistently, processing of pro-caspase-1 induced by alum was abolished in macrophages lacking Nlrp3 or Asc.
100	18624356	Unlike caspase-1 processing and IL-1beta secretion triggered by LPS, alum-mediated activation of the inflammasome did not require exogenous ATP.
101	18624356	Importantly, induction of IgG production against human serum albumin by alum was unimpaired in mice deficient in Nlrp3.
102	18624356	These results indicate that alum induces IL-1beta via the Nlrp3 inflammasome but this activity is dispensable for alum-mediated adjuvant activity.
103	18624356	The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity.
104	18624356	Alum has recently been shown to promote caspase-1 activation and IL-1beta secretion, but the cellular pathways involved remain elusive.
105	18624356	Here we report that the release of IL-1beta triggered by alum is abrogated in macrophages deficient in the NLR family, pyrin domain containing 3 (Nlrp3) protein and the apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) but not the NLR family, CARD domain containing 4 (Nlrc4) protein.
106	18624356	The requirement of the Nlrp3 inflammasome was specific for IL-1beta in that secretion of TNF-alpha was independent of Nlrp3 or Asc.
107	18624356	Consistently, processing of pro-caspase-1 induced by alum was abolished in macrophages lacking Nlrp3 or Asc.
108	18624356	Unlike caspase-1 processing and IL-1beta secretion triggered by LPS, alum-mediated activation of the inflammasome did not require exogenous ATP.
109	18624356	Importantly, induction of IgG production against human serum albumin by alum was unimpaired in mice deficient in Nlrp3.
110	18624356	These results indicate that alum induces IL-1beta via the Nlrp3 inflammasome but this activity is dispensable for alum-mediated adjuvant activity.
111	18779046	The inflammasome is a large multiprotein complex whose assembly leads to the activation of caspase-1, which promotes the maturation of proinflammatory cytokines interleukin-1beta (IL-1beta) and IL-18.
112	19139407	The ability of particulates to promote IL-1beta secretion and caspase 1 activation required particle uptake by DCs and NALP3.
113	19139407	Uptake of microparticles induced lysosomal damage, whereas particle-mediated enhancement of IL-1beta secretion required phagosomal acidification and the lysosomal cysteine protease cathepsin B, suggesting a role for lysosomal damage in inflammasome activation.
114	19428913	It has recently been shown that one member of an intracellular PRR, the NLRP3 inflammasome, is activated by a number of classical adjuvants including aluminum hydroxide and saponins [Eisenbarth SC, Colegio OR, O'Connor W, Sutterwala FS, Flavell RA.
115	19428913	In comparison, NLRP3-deficient and caspase-1-deficient macrophages showed negligible production of IL-1beta.
116	19501527	A number of the NLR family members can form inflammasomes, which are multiprotein complexes that can activate caspase-1 and ultimately lead to the processing and secretion of interleukin (IL)-1beta, IL-18 and IL-33.
117	19543380	Analyses of the cytokine production profile of macrophages isolated from knockout mice deficient in Toll-like receptors (TLRs) or in the adapter molecules MyD88 and TRIF revealed a critical role for TLR2, TLR6 and MyD88 in the production of IFNbeta-independent chemokines.
118	19543380	Reduced expression of RIG-I, MDA-5 and IPS-1 by shRNAs indicated that sensing of MVA by RLR and production of IFNbeta and IFNbeta-dependent chemokines was controlled by the MDA-5 and IPS-1 pathway in the macrophage.
119	19543380	Transcription of the Il1b gene was markedly impaired in TLR2(-/-) and MyD88(-/-) BMDM, whereas mature and secreted IL-1beta was massively reduced in NALP3(-/-) BMDMs or in human THP-1 macrophages with reduced expression of NALP3, ASC or caspase-1 by shRNAs.
120	19543380	Innate immune sensing of MVA and production of chemokines, IFNbeta and IL-1beta by macrophages is mediated by the TLR2-TLR6-MyD88, MDA-5-IPS-1 and NALP3 inflammasome pathways.
121	20921527	Whereas wild-type strains induced low levels of cytokines, an F. tularensis ripA deletion mutant (LVSΔripA) provoked significant release of IL-1β, IL-18, and TNF-α by resting macrophages.
122	20921527	IL-1β and IL-18 secretion was dependent on inflammasome components pyrin-caspase recruitment domain/apoptotic speck-containing protein with a caspase recruitment domain and caspase-1, and the TLR/IL-1R signaling molecule MyD88 was required for inflammatory cytokine synthesis.
123	20921527	The presence of ripA nearly eliminated activation of MAPKs including ERK1/2, JNK, and p38, and pharmacologic inhibitors of these three MAPKs reduced cytokine induction by LVSΔripA.
124	21270336	Here we show that the inflammasome component apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), an adapter protein within the NLRP3 inflammasome, is a crucial element in the adjuvant effect of MF59 when combined with H5N1 subunit vaccines.
125	21270336	In the absence of ASC, H5-specific IgG antibody responses are significantly reduced, whereas the responses are intact in NLRP3(-/-) and caspase-1(-/-) mice.
126	21464087	A miniTUBA dynamic Bayesian network analysis predicted that VTRS1-induced macrophage cell death was mediated by a proinflammatory gene (the tumor necrosis factor alpha [TNF-α] gene), an NF-κB pathway gene (the IκB-α gene), the caspase-2 gene, and several other genes.
127	21464087	Increased production of TNF-α and interleukin 1β (IL-1β) were also detected in the supernatants in VTRS1-infected macrophage cell culture.
128	21464087	VTRS1-induced macrophage cell death was significantly inhibited by a caspase-2 inhibitor but not a caspase-1 inhibitor.
129	21538346	The immunostimulatory properties conferred by vaccine adjuvants require caspase-1 for processing of IL-1β and IL-18.
130	21538346	Listeria monocytogenes is detected in the cytosol by the NLRC4, NLRP3 and AIM2 inflammasomes.
131	21538346	This strain hyperactivated caspase-1 and was preferentially cleared via NLRC4 detection in an IL-1β/IL-18 independent manner.
132	21538346	The immunostimulatory properties conferred by vaccine adjuvants require caspase-1 for processing of IL-1β and IL-18.
133	21538346	Listeria monocytogenes is detected in the cytosol by the NLRC4, NLRP3 and AIM2 inflammasomes.
134	21538346	This strain hyperactivated caspase-1 and was preferentially cleared via NLRC4 detection in an IL-1β/IL-18 independent manner.
135	21540455	Signaling downstream of TLR4 is mediated by the adaptor proteins TRIF [Toll-interleukin-1 (IL-1) receptor (TIR) domain-containing adaptor-inducing interferon-β], which is required for adaptive immune outcomes, and MyD88 (myeloid differentiation marker 88), which is responsible for many proinflammatory effects.
136	21540455	According to the first model, MLA fails to induce maturation of the proinflammatory cytokine IL-1β because it fails to activate caspase-1, which is required for the conversion of pro-IL-1β into its bioactive form.
137	21540455	The second model suggests that MLA triggers unequal engagement of both of the signaling adaptor pathways of TLR4, such that signaling mediated by TRIF is largely intact, whereas signaling mediated by MyD88 is incomplete.
138	21540455	We show that the TRIF-biased signaling that is characteristic of low-toxicity MLA explains its failure to activate caspase-1.
139	21540455	Defective induction of NLRP3, which depends on MyD88, led to decreased assembly of components of the IL-1β-activating inflammasome required for the activation of preformed, inactive procaspase-1.
140	21540455	In addition, we elucidated the contributions of MyD88 and TRIF to priming of the NLRP3 inflammasome and demonstrated that TRIF-biased TLR4 activation by MLA was responsible for the defective production of mature IL-1β.
141	21540455	Signaling downstream of TLR4 is mediated by the adaptor proteins TRIF [Toll-interleukin-1 (IL-1) receptor (TIR) domain-containing adaptor-inducing interferon-β], which is required for adaptive immune outcomes, and MyD88 (myeloid differentiation marker 88), which is responsible for many proinflammatory effects.
142	21540455	According to the first model, MLA fails to induce maturation of the proinflammatory cytokine IL-1β because it fails to activate caspase-1, which is required for the conversion of pro-IL-1β into its bioactive form.
143	21540455	The second model suggests that MLA triggers unequal engagement of both of the signaling adaptor pathways of TLR4, such that signaling mediated by TRIF is largely intact, whereas signaling mediated by MyD88 is incomplete.
144	21540455	We show that the TRIF-biased signaling that is characteristic of low-toxicity MLA explains its failure to activate caspase-1.
145	21540455	Defective induction of NLRP3, which depends on MyD88, led to decreased assembly of components of the IL-1β-activating inflammasome required for the activation of preformed, inactive procaspase-1.
146	21540455	In addition, we elucidated the contributions of MyD88 and TRIF to priming of the NLRP3 inflammasome and demonstrated that TRIF-biased TLR4 activation by MLA was responsible for the defective production of mature IL-1β.
147	21883803	Intracellular bacterial pathogens Francisella novicida and the Live Vaccine Strain (LVS) are recognized in the macrophage cytosol by the AIM2 inflammasome, which leads to the activation of caspase-1 and the processing and secretion of active IL-1β, IL-18 and pyroptosis.
148	22101787	However, during TB, MTB promotes NLRP3- and caspase-1-independent IL-1β release in myeloid cells recruited to lung parenchyma and thus overcomes NLRP3 deficiency in vivo in experimental models.
149	22403439	Caspase-1 has both proinflammatory and regulatory properties in Helicobacter infections, which are differentially mediated by its substrates IL-1β and IL-18.
150	22403439	The proinflammatory cysteine protease caspase-1 is autocatalytically activated upon cytosolic sensing of a variety of pathogen-associated molecular patterns by Nod-like receptors.
151	22403439	Active caspase-1 processes pro-IL-1β and pro-IL-18 to generate the bioactive cytokines and to initiate pathogen-specific immune responses.
152	22403439	We show that caspase-1 is activated and IL-1β and IL-18 are processed in vitro and in vivo as a consequence of Helicobacter infection.
153	22403439	Caspase-1 activation and IL-1 signaling are absolutely required for the efficient control of Helicobacter infection in vaccinated mice.
154	22403439	In conclusion, we show in this study that the processing and release of a regulatory caspase-1 substrate, IL-18, counteracts the proinflammatory activities of another caspase-1 substrate, IL-1β, thereby balancing control of the infection with the prevention of excessive gastric immunopathology.
155	22403439	Caspase-1 has both proinflammatory and regulatory properties in Helicobacter infections, which are differentially mediated by its substrates IL-1β and IL-18.
156	22403439	The proinflammatory cysteine protease caspase-1 is autocatalytically activated upon cytosolic sensing of a variety of pathogen-associated molecular patterns by Nod-like receptors.
157	22403439	Active caspase-1 processes pro-IL-1β and pro-IL-18 to generate the bioactive cytokines and to initiate pathogen-specific immune responses.
158	22403439	We show that caspase-1 is activated and IL-1β and IL-18 are processed in vitro and in vivo as a consequence of Helicobacter infection.
159	22403439	Caspase-1 activation and IL-1 signaling are absolutely required for the efficient control of Helicobacter infection in vaccinated mice.
160	22403439	In conclusion, we show in this study that the processing and release of a regulatory caspase-1 substrate, IL-18, counteracts the proinflammatory activities of another caspase-1 substrate, IL-1β, thereby balancing control of the infection with the prevention of excessive gastric immunopathology.
161	22403439	Caspase-1 has both proinflammatory and regulatory properties in Helicobacter infections, which are differentially mediated by its substrates IL-1β and IL-18.
162	22403439	The proinflammatory cysteine protease caspase-1 is autocatalytically activated upon cytosolic sensing of a variety of pathogen-associated molecular patterns by Nod-like receptors.
163	22403439	Active caspase-1 processes pro-IL-1β and pro-IL-18 to generate the bioactive cytokines and to initiate pathogen-specific immune responses.
164	22403439	We show that caspase-1 is activated and IL-1β and IL-18 are processed in vitro and in vivo as a consequence of Helicobacter infection.
165	22403439	Caspase-1 activation and IL-1 signaling are absolutely required for the efficient control of Helicobacter infection in vaccinated mice.
166	22403439	In conclusion, we show in this study that the processing and release of a regulatory caspase-1 substrate, IL-18, counteracts the proinflammatory activities of another caspase-1 substrate, IL-1β, thereby balancing control of the infection with the prevention of excessive gastric immunopathology.
167	22403439	Caspase-1 has both proinflammatory and regulatory properties in Helicobacter infections, which are differentially mediated by its substrates IL-1β and IL-18.
168	22403439	The proinflammatory cysteine protease caspase-1 is autocatalytically activated upon cytosolic sensing of a variety of pathogen-associated molecular patterns by Nod-like receptors.
169	22403439	Active caspase-1 processes pro-IL-1β and pro-IL-18 to generate the bioactive cytokines and to initiate pathogen-specific immune responses.
170	22403439	We show that caspase-1 is activated and IL-1β and IL-18 are processed in vitro and in vivo as a consequence of Helicobacter infection.
171	22403439	Caspase-1 activation and IL-1 signaling are absolutely required for the efficient control of Helicobacter infection in vaccinated mice.
172	22403439	In conclusion, we show in this study that the processing and release of a regulatory caspase-1 substrate, IL-18, counteracts the proinflammatory activities of another caspase-1 substrate, IL-1β, thereby balancing control of the infection with the prevention of excessive gastric immunopathology.
173	22403439	Caspase-1 has both proinflammatory and regulatory properties in Helicobacter infections, which are differentially mediated by its substrates IL-1β and IL-18.
174	22403439	The proinflammatory cysteine protease caspase-1 is autocatalytically activated upon cytosolic sensing of a variety of pathogen-associated molecular patterns by Nod-like receptors.
175	22403439	Active caspase-1 processes pro-IL-1β and pro-IL-18 to generate the bioactive cytokines and to initiate pathogen-specific immune responses.
176	22403439	We show that caspase-1 is activated and IL-1β and IL-18 are processed in vitro and in vivo as a consequence of Helicobacter infection.
177	22403439	Caspase-1 activation and IL-1 signaling are absolutely required for the efficient control of Helicobacter infection in vaccinated mice.
178	22403439	In conclusion, we show in this study that the processing and release of a regulatory caspase-1 substrate, IL-18, counteracts the proinflammatory activities of another caspase-1 substrate, IL-1β, thereby balancing control of the infection with the prevention of excessive gastric immunopathology.
179	22403439	Caspase-1 has both proinflammatory and regulatory properties in Helicobacter infections, which are differentially mediated by its substrates IL-1β and IL-18.
180	22403439	The proinflammatory cysteine protease caspase-1 is autocatalytically activated upon cytosolic sensing of a variety of pathogen-associated molecular patterns by Nod-like receptors.
181	22403439	Active caspase-1 processes pro-IL-1β and pro-IL-18 to generate the bioactive cytokines and to initiate pathogen-specific immune responses.
182	22403439	We show that caspase-1 is activated and IL-1β and IL-18 are processed in vitro and in vivo as a consequence of Helicobacter infection.
183	22403439	Caspase-1 activation and IL-1 signaling are absolutely required for the efficient control of Helicobacter infection in vaccinated mice.
184	22403439	In conclusion, we show in this study that the processing and release of a regulatory caspase-1 substrate, IL-18, counteracts the proinflammatory activities of another caspase-1 substrate, IL-1β, thereby balancing control of the infection with the prevention of excessive gastric immunopathology.
185	22474329	This elicited inflammasomes, with significant activation of caspase 1, production of IL-1β, and adjuvanticity, demonstrated by enhancing OVA-specific serum IgG antibodies, CD4(+) T cells, and proliferation.
186	22474329	Furthermore, up-regulation of membrane associated IL-15 on DC and CD40L on T cells in the animals treated with alum or the stress agents mediate the interactions between splenic CD11c DC and CD4(+) or CD8(+) T cells.
187	22521247	Imidazoquinoline Toll-like receptor 8 agonists activate human newborn monocytes and dendritic cells through adenosine-refractory and caspase-1-dependent pathways.
188	22674985	Normal human peripheral blood mononuclear cells were used to derive HIV-infected CD4(+) T cell targets and autologous, freshly isolated, natural killer (NK) cells in a novel assay that measures granzyme B (GrB) and HIV-1-infected CD4(+) T cell elimination (ICE) by flow cytometry.
189	22674985	We observed that complex sera mediated greater levels of ADCC than anti-HIV-1 envelope glycoprotein (Env)-specific monoclonal antibodies and serum-mediated ADCC correlated with the amount of IgG and IgG1 bound to HIV-1-infected CD4(+) T cells.
190	22921586	The mycobacterial cord factor trehalose-6,6'-dimycolate (TDM) and its synthetic adjuvant analogue trehalose-6,6'-dibehenate (TDB) rely on the C-type lectin Mincle and the signaling molecules Syk and Card9 to trigger innate immunity.
191	22921586	Additionally, efflux of intracellular potassium, lysosomal rupture, and oxygen radical (ROS) production are crucial for caspase-1 processing and IL-1β secretion by TDB.
192	23056330	Several recent studies have linked vaccine-induced reactogenic side effects to production of the pro-inflammatory cytokine interleukin-1β (IL-1β) in humans.
193	23056330	We found that an rVSV vaccine induced local and systemic production of IL-1β in vivo, and that accumulation of IL-1β correlated with acute pathology after rVSV immunization. rVSV-induced pathology was reduced in mice deficient in the IL-1 receptor Type I, but the IL-1R-/- mice were fully protected from lethal rechallenge with a high dose of VSV.
194	23056330	The amount of IL-1β detected in mice deficient in either caspase-1 or the inflammasome adaptor molecule ASC after rVSV immunization was not significantly different than that produced by wild type animals, and caspase-1-/- and ASC-/- mice were only partially protected from rVSV-induced pathology.
195	23056330	Those data support the idea that some of the IL-1β expressed in vivo in response to VSV may be activated by a caspase-1 and ASC-independent mechanism.
196	23056330	Together these results suggest that rVSV vectors engineered to suppress the induction of IL-1β, or signaling through the IL-1R would be less reactogenic in vivo, but would retain their immunogenicity and protective capacity.
197	23056330	Several recent studies have linked vaccine-induced reactogenic side effects to production of the pro-inflammatory cytokine interleukin-1β (IL-1β) in humans.
198	23056330	We found that an rVSV vaccine induced local and systemic production of IL-1β in vivo, and that accumulation of IL-1β correlated with acute pathology after rVSV immunization. rVSV-induced pathology was reduced in mice deficient in the IL-1 receptor Type I, but the IL-1R-/- mice were fully protected from lethal rechallenge with a high dose of VSV.
199	23056330	The amount of IL-1β detected in mice deficient in either caspase-1 or the inflammasome adaptor molecule ASC after rVSV immunization was not significantly different than that produced by wild type animals, and caspase-1-/- and ASC-/- mice were only partially protected from rVSV-induced pathology.
200	23056330	Those data support the idea that some of the IL-1β expressed in vivo in response to VSV may be activated by a caspase-1 and ASC-independent mechanism.
201	23056330	Together these results suggest that rVSV vectors engineered to suppress the induction of IL-1β, or signaling through the IL-1R would be less reactogenic in vivo, but would retain their immunogenicity and protective capacity.
202	23468632	SIVmac251-infected human reverse transcriptase (hTERT)-transduced CD4(+) T-cell clone targets were co-incubated with autologous macaque effector cells to measure infected CD4(+) T-cell elimination (ICE).
203	23468632	In addition, significant correlations between ICE and viral load (r = -0.57, p = 0.01), and between granzyme B delivery and ICE (r = 0.89, p<0.001) were observed.
204	23468632	These findings support that greater lytic granule loading of virus-specific CD8(+) T cells and efficient delivery of active granzyme B to SIV-infected targets are associated with superior control of SIV infection in rhesus macaques, consistent with observations of HIV infection in humans.
205	23468632	SIVmac251-infected human reverse transcriptase (hTERT)-transduced CD4(+) T-cell clone targets were co-incubated with autologous macaque effector cells to measure infected CD4(+) T-cell elimination (ICE).
206	23468632	In addition, significant correlations between ICE and viral load (r = -0.57, p = 0.01), and between granzyme B delivery and ICE (r = 0.89, p<0.001) were observed.
207	23468632	These findings support that greater lytic granule loading of virus-specific CD8(+) T cells and efficient delivery of active granzyme B to SIV-infected targets are associated with superior control of SIV infection in rhesus macaques, consistent with observations of HIV infection in humans.
208	23603355	An increased release of CCL2/MCP-1 and CXCL1/KC was also observed, resulting in macrophage and neutrophil recruitment in vitro.
209	23603355	Lastly, the incubation of macrophages with KMP-11-loaded PLGA nanoparticles triggered the activation of caspase-1 and the secretion of IL-1β and IL-18, suggesting inflammasome participation.
210	23630357	Cord factor and peptidoglycan recapitulate the Th17-promoting adjuvant activity of mycobacteria through mincle/CARD9 signaling and the inflammasome.
211	23630357	We found that IL-17 secretion by CD4(+) T cells following CFA immunization requires MyD88 and IL-1β/IL-1R signaling.
212	23630357	Through measurement of Ag-specific responses after adoptive transfer of OTII cells, we confirmed that MyD88-dependent signaling controls Th17 differentiation rather than simply production of IL-17.
213	23630357	Additional experiments showed that CFA-induced Th17 differentiation involves IL-1β processing by the inflammasome, as mice lacking caspase-1, ASC, or NLRP3 exhibit partially defective responses after immunization.
214	23630357	By assaying Il1b transcripts in the injection site skin of CFA-immunized mice, we found that signaling through the adaptor molecule caspase activation and recruitment domain 9 (CARD9) plays a major role in triggering pro-IL-1β expression.
215	23630357	Moreover, we demonstrated that recognition of the mycobacterial glycolipid trehalose dimycolate (cord factor) by the C-type lectin receptor mincle partially explains this CARD9 requirement.
216	23630357	Importantly, purified peptidoglycan and cord factor administered in mineral oil synergized to recapitulate the Th17-promoting activity of CFA, and, as expected, this response was diminished in caspase-1- and CARD9-deficient mice.
217	23630357	Cord factor and peptidoglycan recapitulate the Th17-promoting adjuvant activity of mycobacteria through mincle/CARD9 signaling and the inflammasome.
218	23630357	We found that IL-17 secretion by CD4(+) T cells following CFA immunization requires MyD88 and IL-1β/IL-1R signaling.
219	23630357	Through measurement of Ag-specific responses after adoptive transfer of OTII cells, we confirmed that MyD88-dependent signaling controls Th17 differentiation rather than simply production of IL-17.
220	23630357	Additional experiments showed that CFA-induced Th17 differentiation involves IL-1β processing by the inflammasome, as mice lacking caspase-1, ASC, or NLRP3 exhibit partially defective responses after immunization.
221	23630357	By assaying Il1b transcripts in the injection site skin of CFA-immunized mice, we found that signaling through the adaptor molecule caspase activation and recruitment domain 9 (CARD9) plays a major role in triggering pro-IL-1β expression.
222	23630357	Moreover, we demonstrated that recognition of the mycobacterial glycolipid trehalose dimycolate (cord factor) by the C-type lectin receptor mincle partially explains this CARD9 requirement.
223	23630357	Importantly, purified peptidoglycan and cord factor administered in mineral oil synergized to recapitulate the Th17-promoting activity of CFA, and, as expected, this response was diminished in caspase-1- and CARD9-deficient mice.
224	23774604	IL-17 protein levels were also higher in the lungs of mice infected with the LVS rather than F. tularensis type A, while IL-23p19 mRNA expression was found to be caspase-1 dependent in macrophages infected with LVS but not SchuS4.
225	23821549	F. tularensis represses inflammasome; a cytosolic multi-protein complex that activates caspase-1 to produce proinflammatory cytokines IL-1β and IL-18.
226	23821549	We demonstrate that muted IL-1β and IL-18 responses generated in macrophages infected with F. tularensis live vaccine strain (LVS) or the virulent SchuS4 strain are due to a predominant suppressive effect on TLR2-dependent signal 1.
227	23821549	Our results also demonstrate that FTL_0325 of F. tularensis impacts proIL-1β expression as early as 2 h post-infection and delays activation of AIM2 and NLRP3-inflammasomes in a TLR2-dependent fashion.
228	23821549	An enhanced activation of caspase-1 and IL-1β observed in FTL_0325 mutant-infected macrophages at 24 h post-infection was independent of both AIM2 and NLRP3.
229	23821549	F. tularensis represses inflammasome; a cytosolic multi-protein complex that activates caspase-1 to produce proinflammatory cytokines IL-1β and IL-18.
230	23821549	We demonstrate that muted IL-1β and IL-18 responses generated in macrophages infected with F. tularensis live vaccine strain (LVS) or the virulent SchuS4 strain are due to a predominant suppressive effect on TLR2-dependent signal 1.
231	23821549	Our results also demonstrate that FTL_0325 of F. tularensis impacts proIL-1β expression as early as 2 h post-infection and delays activation of AIM2 and NLRP3-inflammasomes in a TLR2-dependent fashion.
232	23821549	An enhanced activation of caspase-1 and IL-1β observed in FTL_0325 mutant-infected macrophages at 24 h post-infection was independent of both AIM2 and NLRP3.
233	23852601	Inflammasome activation and inhibition in primary murine bone marrow-derived cells, and assays for IL-1α, IL-1β, and caspase-1.
234	23852601	Through its ability to control the proteolytic maturation and secretion of interleukin-1 family cytokines, the inflammasome occupies a central role in the activation of inflammation and also influences the shaping of adaptive immunity.
235	23852601	The protocol encompasses cell handling, inflammasome activation and inhibition, as well as the detection of IL-1β, caspase-1, and IL-1α by ELISA and Western blot.
236	23852601	Inflammasome activation and inhibition in primary murine bone marrow-derived cells, and assays for IL-1α, IL-1β, and caspase-1.
237	23852601	Through its ability to control the proteolytic maturation and secretion of interleukin-1 family cytokines, the inflammasome occupies a central role in the activation of inflammation and also influences the shaping of adaptive immunity.
238	23852601	The protocol encompasses cell handling, inflammasome activation and inhibition, as well as the detection of IL-1β, caspase-1, and IL-1α by ELISA and Western blot.
239	24276957	Receptors of the innate immune system including Toll like receptor 5, ICE protease activating factor, and neuronal apoptosis inhibitory protein 5 signal in response to bacterial flagellins.
240	24323452	Protein-bound polysaccharide-K induces IL-1β via TLR2 and NLRP3 inflammasome activation.
241	24323452	Using THP-1 cells, we have demonstrated that PSK induces both pro-IL-1β and mature IL-1β in THP-1 cells in a caspase 1- and NLRP3-dependent manner.
242	24323452	PSK also induces IL-1β and IL-18 in human PBMC.
243	24323452	Cathepsin B is required for PSK-induced inflammasome activation as CA-074-Me, a cathepsin B inhibitor, significantly decreased PSK-induced IL-1β.
244	24323452	Comparison of PSK-induced IL-1β in bone marrow-derived macrophages from wild type C57BL/6 mice, TLR2(-/-), P2X7R(-/-) and NLRP3(-/-) mice demonstrated that PSK-induced IL-1β is dependent on both TLR2 and NLRP3.
245	24323452	P2X7R is not required for PSK-induced inflammasome activation, but enhances PSK-induced caspase-1 activation and IL-1β induction.
246	24323452	Altogether, these results demonstrated that PSK induces inflammasome activation and production of IL-1β in a TLR2- and NLRP3-dependent mechanism.
247	24323452	Protein-bound polysaccharide-K induces IL-1β via TLR2 and NLRP3 inflammasome activation.
248	24323452	Using THP-1 cells, we have demonstrated that PSK induces both pro-IL-1β and mature IL-1β in THP-1 cells in a caspase 1- and NLRP3-dependent manner.
249	24323452	PSK also induces IL-1β and IL-18 in human PBMC.
250	24323452	Cathepsin B is required for PSK-induced inflammasome activation as CA-074-Me, a cathepsin B inhibitor, significantly decreased PSK-induced IL-1β.
251	24323452	Comparison of PSK-induced IL-1β in bone marrow-derived macrophages from wild type C57BL/6 mice, TLR2(-/-), P2X7R(-/-) and NLRP3(-/-) mice demonstrated that PSK-induced IL-1β is dependent on both TLR2 and NLRP3.
252	24323452	P2X7R is not required for PSK-induced inflammasome activation, but enhances PSK-induced caspase-1 activation and IL-1β induction.
253	24323452	Altogether, these results demonstrated that PSK induces inflammasome activation and production of IL-1β in a TLR2- and NLRP3-dependent mechanism.
254	24350060	Previously we demonstrated that live attenuated cattle vaccine strain Brucella abortus RB51 induces caspase-2-mediated and caspase-1-independent PCD of infected macrophages.
255	24350060	We also discovered that rough attenuated B. suis strain VTRS1 induces a caspase-2-mediated and caspase-1-independent proinflammatory cell death in infected macrophages, which was tentatively coined "caspase-2-mediated pyroptosis".
256	24350060	Caspase-2 regulated mitochondrial cytochrome c release and TNFα production, both of which are known to activate caspase-3 and caspase-8, respectively.
257	24350060	In addition to TNFα, RB51-induced caspase-1 and IL-1β production was also driven by caspase-2-mediated mitochondrial dysfunction.
258	24350060	Our data suggest that caspase-2 acts as an initiator caspase that mediates a novel RB51-induced hybrid cell death that simulates but differs from typical non-proinflammatory apoptosis and caspase-1-mediated proinflammatory pyroptosis.
259	24350060	Caspase-2 also regulated caspase-3 and -8 activation, as well as cell death in macrophages treated with each of the three reagents.
260	24350060	Previously we demonstrated that live attenuated cattle vaccine strain Brucella abortus RB51 induces caspase-2-mediated and caspase-1-independent PCD of infected macrophages.
261	24350060	We also discovered that rough attenuated B. suis strain VTRS1 induces a caspase-2-mediated and caspase-1-independent proinflammatory cell death in infected macrophages, which was tentatively coined "caspase-2-mediated pyroptosis".
262	24350060	Caspase-2 regulated mitochondrial cytochrome c release and TNFα production, both of which are known to activate caspase-3 and caspase-8, respectively.
263	24350060	In addition to TNFα, RB51-induced caspase-1 and IL-1β production was also driven by caspase-2-mediated mitochondrial dysfunction.
264	24350060	Our data suggest that caspase-2 acts as an initiator caspase that mediates a novel RB51-induced hybrid cell death that simulates but differs from typical non-proinflammatory apoptosis and caspase-1-mediated proinflammatory pyroptosis.
265	24350060	Caspase-2 also regulated caspase-3 and -8 activation, as well as cell death in macrophages treated with each of the three reagents.
266	24350060	Previously we demonstrated that live attenuated cattle vaccine strain Brucella abortus RB51 induces caspase-2-mediated and caspase-1-independent PCD of infected macrophages.
267	24350060	We also discovered that rough attenuated B. suis strain VTRS1 induces a caspase-2-mediated and caspase-1-independent proinflammatory cell death in infected macrophages, which was tentatively coined "caspase-2-mediated pyroptosis".
268	24350060	Caspase-2 regulated mitochondrial cytochrome c release and TNFα production, both of which are known to activate caspase-3 and caspase-8, respectively.
269	24350060	In addition to TNFα, RB51-induced caspase-1 and IL-1β production was also driven by caspase-2-mediated mitochondrial dysfunction.
270	24350060	Our data suggest that caspase-2 acts as an initiator caspase that mediates a novel RB51-induced hybrid cell death that simulates but differs from typical non-proinflammatory apoptosis and caspase-1-mediated proinflammatory pyroptosis.
271	24350060	Caspase-2 also regulated caspase-3 and -8 activation, as well as cell death in macrophages treated with each of the three reagents.
272	24350060	Previously we demonstrated that live attenuated cattle vaccine strain Brucella abortus RB51 induces caspase-2-mediated and caspase-1-independent PCD of infected macrophages.
273	24350060	We also discovered that rough attenuated B. suis strain VTRS1 induces a caspase-2-mediated and caspase-1-independent proinflammatory cell death in infected macrophages, which was tentatively coined "caspase-2-mediated pyroptosis".
274	24350060	Caspase-2 regulated mitochondrial cytochrome c release and TNFα production, both of which are known to activate caspase-3 and caspase-8, respectively.
275	24350060	In addition to TNFα, RB51-induced caspase-1 and IL-1β production was also driven by caspase-2-mediated mitochondrial dysfunction.
276	24350060	Our data suggest that caspase-2 acts as an initiator caspase that mediates a novel RB51-induced hybrid cell death that simulates but differs from typical non-proinflammatory apoptosis and caspase-1-mediated proinflammatory pyroptosis.
277	24350060	Caspase-2 also regulated caspase-3 and -8 activation, as well as cell death in macrophages treated with each of the three reagents.
278	24610009	Like other particulate vaccine adjuvants, IMX potently activated the NALP-3-ASC-Caspase-1 inflammasome in APCs, leading to IL-1β and IL-18 production.
279	24799678	Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death.
280	24799678	The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF.
281	24799678	Here we provide genetic evidence for a receptor-interacting protein (RIP) kinase-caspase-8-dependent macrophage apoptotic death pathway after infection with Y. pestis, influenced by Toll-like receptor 4-TIR-domain-containing adapter-inducing interferon-β (TLR4-TRIF).
282	24799678	Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1β, IL-18, TNF, and IL-6; impaired activation of the transcription factor NF-κB; and greatly compromised caspase-1 processing.
283	24799678	Cleavage of the proform of caspase-1 is associated with triggering inflammasome activity, which leads to the maturation of IL-1β and IL-18, cytokines important to host responses against Y. pestis and many other infectious agents.
284	24799678	Our results identify a RIP1-caspase-8/RIP3-dependent caspase-1 activation pathway after Y. pestis challenge.
285	24799678	Mice defective in caspase-8 and RIP3 were also highly susceptible to infection and displayed reduced proinflammatory cytokines and myeloid cell death.
286	24799678	We propose that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis infection.
287	24799678	Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death.
288	24799678	The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF.
289	24799678	Here we provide genetic evidence for a receptor-interacting protein (RIP) kinase-caspase-8-dependent macrophage apoptotic death pathway after infection with Y. pestis, influenced by Toll-like receptor 4-TIR-domain-containing adapter-inducing interferon-β (TLR4-TRIF).
290	24799678	Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1β, IL-18, TNF, and IL-6; impaired activation of the transcription factor NF-κB; and greatly compromised caspase-1 processing.
291	24799678	Cleavage of the proform of caspase-1 is associated with triggering inflammasome activity, which leads to the maturation of IL-1β and IL-18, cytokines important to host responses against Y. pestis and many other infectious agents.
292	24799678	Our results identify a RIP1-caspase-8/RIP3-dependent caspase-1 activation pathway after Y. pestis challenge.
293	24799678	Mice defective in caspase-8 and RIP3 were also highly susceptible to infection and displayed reduced proinflammatory cytokines and myeloid cell death.
294	24799678	We propose that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis infection.
295	24799678	Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death.
296	24799678	The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF.
297	24799678	Here we provide genetic evidence for a receptor-interacting protein (RIP) kinase-caspase-8-dependent macrophage apoptotic death pathway after infection with Y. pestis, influenced by Toll-like receptor 4-TIR-domain-containing adapter-inducing interferon-β (TLR4-TRIF).
298	24799678	Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1β, IL-18, TNF, and IL-6; impaired activation of the transcription factor NF-κB; and greatly compromised caspase-1 processing.
299	24799678	Cleavage of the proform of caspase-1 is associated with triggering inflammasome activity, which leads to the maturation of IL-1β and IL-18, cytokines important to host responses against Y. pestis and many other infectious agents.
300	24799678	Our results identify a RIP1-caspase-8/RIP3-dependent caspase-1 activation pathway after Y. pestis challenge.
301	24799678	Mice defective in caspase-8 and RIP3 were also highly susceptible to infection and displayed reduced proinflammatory cytokines and myeloid cell death.
302	24799678	We propose that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis infection.
303	24799678	Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death.
304	24799678	The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF.
305	24799678	Here we provide genetic evidence for a receptor-interacting protein (RIP) kinase-caspase-8-dependent macrophage apoptotic death pathway after infection with Y. pestis, influenced by Toll-like receptor 4-TIR-domain-containing adapter-inducing interferon-β (TLR4-TRIF).
306	24799678	Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1β, IL-18, TNF, and IL-6; impaired activation of the transcription factor NF-κB; and greatly compromised caspase-1 processing.
307	24799678	Cleavage of the proform of caspase-1 is associated with triggering inflammasome activity, which leads to the maturation of IL-1β and IL-18, cytokines important to host responses against Y. pestis and many other infectious agents.
308	24799678	Our results identify a RIP1-caspase-8/RIP3-dependent caspase-1 activation pathway after Y. pestis challenge.
309	24799678	Mice defective in caspase-8 and RIP3 were also highly susceptible to infection and displayed reduced proinflammatory cytokines and myeloid cell death.
310	24799678	We propose that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis infection.
311	24898077	However, IL-18 protein lacks a typical signal sequence and requires cleavage into its mature active form by caspase 1.
312	24898077	In this study, we constructed mammalian expression vectors carrying cDNA encoding mature canine IL-18 (cIL-18) or mouse IL-18 (mIL-18) fused to the human IL-2 (hIL-2) signal sequence.
313	24898077	Using reverse genetics, we also generated a recombinant canine distemper virus that expresses cIL-18 or mIL-18 fused to the hIL-2 signal sequence.
314	24898077	These results indicate that the signal sequence from hIL-2 is suitable for the secretion of mature IL-18.
315	24955107	The inflammasome refers to a protein complex that functions as an activation platform for the cysteine protease caspase-1, which then processes inflammatory molecules such as IL-1β and IL-18 into functional forms.
316	24955107	Secretion of IL-1β and IL-18 are important components of antimicrobial immunity and, as a result, pathogens have evolved factors to evade or counteract this response.
317	25063877	Caspase-8 modulates dectin-1 and complement receptor 3-driven IL-1β production in response to β-glucans and the fungal pathogen, Candida albicans.
318	25063877	The nucleotide-binding domain and leucine-rich repeat containing family (NLR), pyrin domain-containing 3 (NLRP3) inflammasome plays a key role in triggering caspase-1-dependent IL-1β maturation and resistance to fungal dissemination in Candida albicans infection. β-Glucans are major components of fungal cell walls that trigger IL-1β secretion in both murine and human immune cells.
319	25063877	We show that the NLRP3-apoptosis-associated speck-like protein containing caspase recruitment domain protein-caspase-1 inflammasome is absolutely critical for IL-1β production in response to β-glucans.
320	25063877	Interestingly, we also found that both complement receptor 3 (CR3) and dectin-1 play a crucial role in coordinating β-glucan-induced IL-1β processing as well as a cell death response.
321	25063877	In addition to the essential role of caspase-1, we identify an important role for the proapoptotic protease caspase-8 in promoting β-glucan-induced cell death and NLRP3 inflammasome-dependent IL-1β maturation.
322	25063877	A strong requirement for CR3 and caspase-8 also was found for NLRP3-dependent IL-1β production in response to heat-killed C. albicans.
323	25063877	Taken together, these results define the importance of dectin-1, CR3, and caspase-8, in addition to the canonical NLRP3 inflammasome, in mediating β-glucan- and C. albicans-induced innate responses in dendritic cells.
324	25063877	Collectively, these findings establish a novel link between β-glucan recognition receptors and the inflammatory proteases caspase-8 and caspase-1 in coordinating cytokine secretion and cell death in response to immunostimulatory fungal components.
325	25063877	Caspase-8 modulates dectin-1 and complement receptor 3-driven IL-1β production in response to β-glucans and the fungal pathogen, Candida albicans.
326	25063877	The nucleotide-binding domain and leucine-rich repeat containing family (NLR), pyrin domain-containing 3 (NLRP3) inflammasome plays a key role in triggering caspase-1-dependent IL-1β maturation and resistance to fungal dissemination in Candida albicans infection. β-Glucans are major components of fungal cell walls that trigger IL-1β secretion in both murine and human immune cells.
327	25063877	We show that the NLRP3-apoptosis-associated speck-like protein containing caspase recruitment domain protein-caspase-1 inflammasome is absolutely critical for IL-1β production in response to β-glucans.
328	25063877	Interestingly, we also found that both complement receptor 3 (CR3) and dectin-1 play a crucial role in coordinating β-glucan-induced IL-1β processing as well as a cell death response.
329	25063877	In addition to the essential role of caspase-1, we identify an important role for the proapoptotic protease caspase-8 in promoting β-glucan-induced cell death and NLRP3 inflammasome-dependent IL-1β maturation.
330	25063877	A strong requirement for CR3 and caspase-8 also was found for NLRP3-dependent IL-1β production in response to heat-killed C. albicans.
331	25063877	Taken together, these results define the importance of dectin-1, CR3, and caspase-8, in addition to the canonical NLRP3 inflammasome, in mediating β-glucan- and C. albicans-induced innate responses in dendritic cells.
332	25063877	Collectively, these findings establish a novel link between β-glucan recognition receptors and the inflammatory proteases caspase-8 and caspase-1 in coordinating cytokine secretion and cell death in response to immunostimulatory fungal components.
333	25063877	Caspase-8 modulates dectin-1 and complement receptor 3-driven IL-1β production in response to β-glucans and the fungal pathogen, Candida albicans.
334	25063877	The nucleotide-binding domain and leucine-rich repeat containing family (NLR), pyrin domain-containing 3 (NLRP3) inflammasome plays a key role in triggering caspase-1-dependent IL-1β maturation and resistance to fungal dissemination in Candida albicans infection. β-Glucans are major components of fungal cell walls that trigger IL-1β secretion in both murine and human immune cells.
335	25063877	We show that the NLRP3-apoptosis-associated speck-like protein containing caspase recruitment domain protein-caspase-1 inflammasome is absolutely critical for IL-1β production in response to β-glucans.
336	25063877	Interestingly, we also found that both complement receptor 3 (CR3) and dectin-1 play a crucial role in coordinating β-glucan-induced IL-1β processing as well as a cell death response.
337	25063877	In addition to the essential role of caspase-1, we identify an important role for the proapoptotic protease caspase-8 in promoting β-glucan-induced cell death and NLRP3 inflammasome-dependent IL-1β maturation.
338	25063877	A strong requirement for CR3 and caspase-8 also was found for NLRP3-dependent IL-1β production in response to heat-killed C. albicans.
339	25063877	Taken together, these results define the importance of dectin-1, CR3, and caspase-8, in addition to the canonical NLRP3 inflammasome, in mediating β-glucan- and C. albicans-induced innate responses in dendritic cells.
340	25063877	Collectively, these findings establish a novel link between β-glucan recognition receptors and the inflammatory proteases caspase-8 and caspase-1 in coordinating cytokine secretion and cell death in response to immunostimulatory fungal components.
341	25063877	Caspase-8 modulates dectin-1 and complement receptor 3-driven IL-1β production in response to β-glucans and the fungal pathogen, Candida albicans.
342	25063877	The nucleotide-binding domain and leucine-rich repeat containing family (NLR), pyrin domain-containing 3 (NLRP3) inflammasome plays a key role in triggering caspase-1-dependent IL-1β maturation and resistance to fungal dissemination in Candida albicans infection. β-Glucans are major components of fungal cell walls that trigger IL-1β secretion in both murine and human immune cells.
343	25063877	We show that the NLRP3-apoptosis-associated speck-like protein containing caspase recruitment domain protein-caspase-1 inflammasome is absolutely critical for IL-1β production in response to β-glucans.
344	25063877	Interestingly, we also found that both complement receptor 3 (CR3) and dectin-1 play a crucial role in coordinating β-glucan-induced IL-1β processing as well as a cell death response.
345	25063877	In addition to the essential role of caspase-1, we identify an important role for the proapoptotic protease caspase-8 in promoting β-glucan-induced cell death and NLRP3 inflammasome-dependent IL-1β maturation.
346	25063877	A strong requirement for CR3 and caspase-8 also was found for NLRP3-dependent IL-1β production in response to heat-killed C. albicans.
347	25063877	Taken together, these results define the importance of dectin-1, CR3, and caspase-8, in addition to the canonical NLRP3 inflammasome, in mediating β-glucan- and C. albicans-induced innate responses in dendritic cells.
348	25063877	Collectively, these findings establish a novel link between β-glucan recognition receptors and the inflammatory proteases caspase-8 and caspase-1 in coordinating cytokine secretion and cell death in response to immunostimulatory fungal components.
349	25223833	The protective effect of the FliCi+P10 formulation required TLR-5, myeloid differentiation primary response gene 88 and IFN-γ expression, but caspase-1 knockout mice were only partially protected, suggesting that intracellular flagellin receptors are not involved with the anti-tumor effect.
350	25448112	We here show that incubation of monocytes with the PmpG-1-vaults activates caspase-1 and stimulates IL-1β secretion through a process requiring the NLRP3 inflammasome and that cathepsin B and Syk are involved in the inflammasome activation.
351	25786687	Cholera toxin, and the related nontoxic adjuvants mmCT and dmLT, promote human Th17 responses via cyclic AMP-protein kinase A and inflammasome-dependent IL-1 signaling.
352	25786687	CT, mmCT, and dmLT strongly enhanced IL-17A and to a lesser extent IL-13 responses, but had little effect on IFN-γ production or cell proliferation.
353	25786687	Intracellular cytokine staining revealed that the enhanced IL-17A production was largely confined to CD4(+) T cells and coculture experiments showed that the IL-17A promotion was effectively induced by adjuvant-treated monocytes.
354	25786687	Thus, inhibition of cAMP-dependent protein kinase A was abolished, and stimulation with a cAMP analog mimicked the adjuvant effect.
355	25786687	Furthermore, CT, mmCT, and dmLT induced IL-1β production and caspase-1 activation in monocytes, which was associated with increased expression of key proinflammatory and inflammasome-related genes, including NLRP1, NLRP3, and NLRC4.
356	25786687	Inflammasome inhibition with a specific caspase-1 inhibitor, or blocking of IL-1 signaling by IL-1 receptor antagonist, abrogated the Th17-promoting effect.
357	25786687	We conclude that CT, mmCT, and dmLT promote human Th17 responses via cAMP-dependent protein kinase A and caspase-1/inflammasome-dependent IL-1 signaling.
358	25786687	Cholera toxin, and the related nontoxic adjuvants mmCT and dmLT, promote human Th17 responses via cyclic AMP-protein kinase A and inflammasome-dependent IL-1 signaling.
359	25786687	CT, mmCT, and dmLT strongly enhanced IL-17A and to a lesser extent IL-13 responses, but had little effect on IFN-γ production or cell proliferation.
360	25786687	Intracellular cytokine staining revealed that the enhanced IL-17A production was largely confined to CD4(+) T cells and coculture experiments showed that the IL-17A promotion was effectively induced by adjuvant-treated monocytes.
361	25786687	Thus, inhibition of cAMP-dependent protein kinase A was abolished, and stimulation with a cAMP analog mimicked the adjuvant effect.
362	25786687	Furthermore, CT, mmCT, and dmLT induced IL-1β production and caspase-1 activation in monocytes, which was associated with increased expression of key proinflammatory and inflammasome-related genes, including NLRP1, NLRP3, and NLRC4.
363	25786687	Inflammasome inhibition with a specific caspase-1 inhibitor, or blocking of IL-1 signaling by IL-1 receptor antagonist, abrogated the Th17-promoting effect.
364	25786687	We conclude that CT, mmCT, and dmLT promote human Th17 responses via cAMP-dependent protein kinase A and caspase-1/inflammasome-dependent IL-1 signaling.
365	25786687	Cholera toxin, and the related nontoxic adjuvants mmCT and dmLT, promote human Th17 responses via cyclic AMP-protein kinase A and inflammasome-dependent IL-1 signaling.
366	25786687	CT, mmCT, and dmLT strongly enhanced IL-17A and to a lesser extent IL-13 responses, but had little effect on IFN-γ production or cell proliferation.
367	25786687	Intracellular cytokine staining revealed that the enhanced IL-17A production was largely confined to CD4(+) T cells and coculture experiments showed that the IL-17A promotion was effectively induced by adjuvant-treated monocytes.
368	25786687	Thus, inhibition of cAMP-dependent protein kinase A was abolished, and stimulation with a cAMP analog mimicked the adjuvant effect.
369	25786687	Furthermore, CT, mmCT, and dmLT induced IL-1β production and caspase-1 activation in monocytes, which was associated with increased expression of key proinflammatory and inflammasome-related genes, including NLRP1, NLRP3, and NLRC4.
370	25786687	Inflammasome inhibition with a specific caspase-1 inhibitor, or blocking of IL-1 signaling by IL-1 receptor antagonist, abrogated the Th17-promoting effect.
371	25786687	We conclude that CT, mmCT, and dmLT promote human Th17 responses via cAMP-dependent protein kinase A and caspase-1/inflammasome-dependent IL-1 signaling.
372	26032420	Spleen Tyrosine Kinase (Syk) Mediates IL-1β Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection.
373	26032420	Syk induces elevated IL1B, TNF, and IL6 mRNA by 2 hpi.
374	26032420	Syk mediates elevated IL-1β secretion by activating ERK1/2, and both Syk and ERK1/2 inhibitors ablated ADE-induced IL-1β secretion.
375	26032420	Maturation of pro-IL-1β during ADE requires caspase-1 and NLRP3, but caspase-1 is suboptimally increased by ADE and can be significantly enhanced by a typical inflammasome agonist, ATP.
376	26032420	Importantly, this inflammatory Syk-ERK signaling axis requires DENV immune complexes, because DENV-2 in the presence of serotype-matched anti-DENV-2 mAb, but not anti-DENV-1 mAb, activates Syk, ERK, and IL-1β secretion.
377	26032420	Syk and ERK may serve as new therapeutic targets for interfering with ADE-induced cytokine expression during severe dengue.
378	26100631	We recently described the induction of noncanonical IL-1β processing via caspase-8 recruited to ripoptosome signaling platforms in myeloid leukocytes.
379	26100631	Here, we demonstrate that activated NLRP3·ASC inflammasomes recruit caspase-8 to drive IL-1β processing in murine bone marrow-derived dendritic cells (BMDC) independent of caspase-1 and -11.
380	26100631	Sustained stimulation (>2 h) of LPS-primed caspase-1-deficient (Casp1/11(-/-)) BMDC with the canonical NLRP3 inflammasome agonist nigericin results in release of bioactive IL-1β in conjunction with robust caspase-8 activation.
381	26100631	This IL-1β processing and caspase-8 activation do not proceed in Nlrp3(-/-) or Asc(-/-) BMDC and are suppressed by pharmacological inhibition of caspase-8, indicating that caspase-8 can act as a direct IL-1β-converting enzyme during NLRP3 inflammasome activation.
382	26100631	Biochemical analyses of WT and Casp1/11(-/-) BMDC indicated that caspase-8 is proteolytically processed within detergent-insoluble ASC-enriched protein complexes prior to extracellular export during nigericin treatment.
383	26100631	Although nigericin-stimulated caspase-1 activation and activity are only modestly attenuated in caspase-8-deficient (Casp8(-/-)Rip3(-/-)) BMDC, these cells do not exhibit the rapid loss of viability of WT cells.
384	26100631	These results support a contribution of caspase-8 to both IL-1β production and regulated death signaling via NLRP3 inflammasomes.
385	26100631	In the absence of caspase-1, NLRP3 inflammasomes directly utilize caspase-8 as both a pro-apoptotic initiator and major IL-1β-converting protease.
386	26100631	In the presence of caspase-1, caspase-8 acts as a positive modulator of the NLRP3-dependent caspase-1 signaling cascades that drive both IL-1β production and pyroptotic death.
387	26100631	We recently described the induction of noncanonical IL-1β processing via caspase-8 recruited to ripoptosome signaling platforms in myeloid leukocytes.
388	26100631	Here, we demonstrate that activated NLRP3·ASC inflammasomes recruit caspase-8 to drive IL-1β processing in murine bone marrow-derived dendritic cells (BMDC) independent of caspase-1 and -11.
389	26100631	Sustained stimulation (>2 h) of LPS-primed caspase-1-deficient (Casp1/11(-/-)) BMDC with the canonical NLRP3 inflammasome agonist nigericin results in release of bioactive IL-1β in conjunction with robust caspase-8 activation.
390	26100631	This IL-1β processing and caspase-8 activation do not proceed in Nlrp3(-/-) or Asc(-/-) BMDC and are suppressed by pharmacological inhibition of caspase-8, indicating that caspase-8 can act as a direct IL-1β-converting enzyme during NLRP3 inflammasome activation.
391	26100631	Biochemical analyses of WT and Casp1/11(-/-) BMDC indicated that caspase-8 is proteolytically processed within detergent-insoluble ASC-enriched protein complexes prior to extracellular export during nigericin treatment.
392	26100631	Although nigericin-stimulated caspase-1 activation and activity are only modestly attenuated in caspase-8-deficient (Casp8(-/-)Rip3(-/-)) BMDC, these cells do not exhibit the rapid loss of viability of WT cells.
393	26100631	These results support a contribution of caspase-8 to both IL-1β production and regulated death signaling via NLRP3 inflammasomes.
394	26100631	In the absence of caspase-1, NLRP3 inflammasomes directly utilize caspase-8 as both a pro-apoptotic initiator and major IL-1β-converting protease.
395	26100631	In the presence of caspase-1, caspase-8 acts as a positive modulator of the NLRP3-dependent caspase-1 signaling cascades that drive both IL-1β production and pyroptotic death.
396	26100631	We recently described the induction of noncanonical IL-1β processing via caspase-8 recruited to ripoptosome signaling platforms in myeloid leukocytes.
397	26100631	Here, we demonstrate that activated NLRP3·ASC inflammasomes recruit caspase-8 to drive IL-1β processing in murine bone marrow-derived dendritic cells (BMDC) independent of caspase-1 and -11.
398	26100631	Sustained stimulation (>2 h) of LPS-primed caspase-1-deficient (Casp1/11(-/-)) BMDC with the canonical NLRP3 inflammasome agonist nigericin results in release of bioactive IL-1β in conjunction with robust caspase-8 activation.
399	26100631	This IL-1β processing and caspase-8 activation do not proceed in Nlrp3(-/-) or Asc(-/-) BMDC and are suppressed by pharmacological inhibition of caspase-8, indicating that caspase-8 can act as a direct IL-1β-converting enzyme during NLRP3 inflammasome activation.
400	26100631	Biochemical analyses of WT and Casp1/11(-/-) BMDC indicated that caspase-8 is proteolytically processed within detergent-insoluble ASC-enriched protein complexes prior to extracellular export during nigericin treatment.
401	26100631	Although nigericin-stimulated caspase-1 activation and activity are only modestly attenuated in caspase-8-deficient (Casp8(-/-)Rip3(-/-)) BMDC, these cells do not exhibit the rapid loss of viability of WT cells.
402	26100631	These results support a contribution of caspase-8 to both IL-1β production and regulated death signaling via NLRP3 inflammasomes.
403	26100631	In the absence of caspase-1, NLRP3 inflammasomes directly utilize caspase-8 as both a pro-apoptotic initiator and major IL-1β-converting protease.
404	26100631	In the presence of caspase-1, caspase-8 acts as a positive modulator of the NLRP3-dependent caspase-1 signaling cascades that drive both IL-1β production and pyroptotic death.
405	26100631	We recently described the induction of noncanonical IL-1β processing via caspase-8 recruited to ripoptosome signaling platforms in myeloid leukocytes.
406	26100631	Here, we demonstrate that activated NLRP3·ASC inflammasomes recruit caspase-8 to drive IL-1β processing in murine bone marrow-derived dendritic cells (BMDC) independent of caspase-1 and -11.
407	26100631	Sustained stimulation (>2 h) of LPS-primed caspase-1-deficient (Casp1/11(-/-)) BMDC with the canonical NLRP3 inflammasome agonist nigericin results in release of bioactive IL-1β in conjunction with robust caspase-8 activation.
408	26100631	This IL-1β processing and caspase-8 activation do not proceed in Nlrp3(-/-) or Asc(-/-) BMDC and are suppressed by pharmacological inhibition of caspase-8, indicating that caspase-8 can act as a direct IL-1β-converting enzyme during NLRP3 inflammasome activation.
409	26100631	Biochemical analyses of WT and Casp1/11(-/-) BMDC indicated that caspase-8 is proteolytically processed within detergent-insoluble ASC-enriched protein complexes prior to extracellular export during nigericin treatment.
410	26100631	Although nigericin-stimulated caspase-1 activation and activity are only modestly attenuated in caspase-8-deficient (Casp8(-/-)Rip3(-/-)) BMDC, these cells do not exhibit the rapid loss of viability of WT cells.
411	26100631	These results support a contribution of caspase-8 to both IL-1β production and regulated death signaling via NLRP3 inflammasomes.
412	26100631	In the absence of caspase-1, NLRP3 inflammasomes directly utilize caspase-8 as both a pro-apoptotic initiator and major IL-1β-converting protease.
413	26100631	In the presence of caspase-1, caspase-8 acts as a positive modulator of the NLRP3-dependent caspase-1 signaling cascades that drive both IL-1β production and pyroptotic death.
414	26100631	We recently described the induction of noncanonical IL-1β processing via caspase-8 recruited to ripoptosome signaling platforms in myeloid leukocytes.
415	26100631	Here, we demonstrate that activated NLRP3·ASC inflammasomes recruit caspase-8 to drive IL-1β processing in murine bone marrow-derived dendritic cells (BMDC) independent of caspase-1 and -11.
416	26100631	Sustained stimulation (>2 h) of LPS-primed caspase-1-deficient (Casp1/11(-/-)) BMDC with the canonical NLRP3 inflammasome agonist nigericin results in release of bioactive IL-1β in conjunction with robust caspase-8 activation.
417	26100631	This IL-1β processing and caspase-8 activation do not proceed in Nlrp3(-/-) or Asc(-/-) BMDC and are suppressed by pharmacological inhibition of caspase-8, indicating that caspase-8 can act as a direct IL-1β-converting enzyme during NLRP3 inflammasome activation.
418	26100631	Biochemical analyses of WT and Casp1/11(-/-) BMDC indicated that caspase-8 is proteolytically processed within detergent-insoluble ASC-enriched protein complexes prior to extracellular export during nigericin treatment.
419	26100631	Although nigericin-stimulated caspase-1 activation and activity are only modestly attenuated in caspase-8-deficient (Casp8(-/-)Rip3(-/-)) BMDC, these cells do not exhibit the rapid loss of viability of WT cells.
420	26100631	These results support a contribution of caspase-8 to both IL-1β production and regulated death signaling via NLRP3 inflammasomes.
421	26100631	In the absence of caspase-1, NLRP3 inflammasomes directly utilize caspase-8 as both a pro-apoptotic initiator and major IL-1β-converting protease.
422	26100631	In the presence of caspase-1, caspase-8 acts as a positive modulator of the NLRP3-dependent caspase-1 signaling cascades that drive both IL-1β production and pyroptotic death.
423	26100631	We recently described the induction of noncanonical IL-1β processing via caspase-8 recruited to ripoptosome signaling platforms in myeloid leukocytes.
424	26100631	Here, we demonstrate that activated NLRP3·ASC inflammasomes recruit caspase-8 to drive IL-1β processing in murine bone marrow-derived dendritic cells (BMDC) independent of caspase-1 and -11.
425	26100631	Sustained stimulation (>2 h) of LPS-primed caspase-1-deficient (Casp1/11(-/-)) BMDC with the canonical NLRP3 inflammasome agonist nigericin results in release of bioactive IL-1β in conjunction with robust caspase-8 activation.
426	26100631	This IL-1β processing and caspase-8 activation do not proceed in Nlrp3(-/-) or Asc(-/-) BMDC and are suppressed by pharmacological inhibition of caspase-8, indicating that caspase-8 can act as a direct IL-1β-converting enzyme during NLRP3 inflammasome activation.
427	26100631	Biochemical analyses of WT and Casp1/11(-/-) BMDC indicated that caspase-8 is proteolytically processed within detergent-insoluble ASC-enriched protein complexes prior to extracellular export during nigericin treatment.
428	26100631	Although nigericin-stimulated caspase-1 activation and activity are only modestly attenuated in caspase-8-deficient (Casp8(-/-)Rip3(-/-)) BMDC, these cells do not exhibit the rapid loss of viability of WT cells.
429	26100631	These results support a contribution of caspase-8 to both IL-1β production and regulated death signaling via NLRP3 inflammasomes.
430	26100631	In the absence of caspase-1, NLRP3 inflammasomes directly utilize caspase-8 as both a pro-apoptotic initiator and major IL-1β-converting protease.
431	26100631	In the presence of caspase-1, caspase-8 acts as a positive modulator of the NLRP3-dependent caspase-1 signaling cascades that drive both IL-1β production and pyroptotic death.
432	26259586	Similar to mice with complete MyD88 deficiency, specific deletion of MyD88 in DCs resulted in a 50-60% reduction in short-term accumulation of both CD103(+)CD11b(+) and CD103(+)CD11b(-) DCs in the MLN.
433	26259586	DC migration was independent of caspase-1, which is responsible for the inflammasome-dependent proteolytic activation of IL-1 cytokine family members, and was not affected by treatment with broad-spectrum antibiotics.
434	26301593	However, IL-1β secretion did require NLRP3 and caspase-1 activity.
435	26301593	We excluded RNA, DNA, contaminating LPS, viral NS1 protein, complement, and cytokines.
436	26344742	Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP.
437	26344742	We have recently reported that intramuscular injection of PCEP induces NLRP3, an inflammasome receptor gene, and inflammatory cytokines, including IL-1β and IL-18, in mouse muscle tissue.
438	26344742	Caspase-1 is required for the processing of pro-forms of IL-1β and IL-18 into mature forms and is a critical constituent of the NLRP3 inflammasome.
439	26344742	Hence, in the present study, we investigated the role of caspase-1 in the secretion of IL-1β and IL-18 in PCEP-stimulated splenic dendritic cells (DCs).
440	26344742	Caspase inhibitor YVAD-fmk-treated splenic DCs showed significantly reduced IL-1β and IL-18 secretion in response to PCEP stimulation.
441	26344742	Further, PCEP had no effect on the expression of MHC class II or co-stimulatory molecules, CD86 and CD40, suggesting that PCEP does not induce DC maturation.
442	26344742	Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP.
443	26344742	We have recently reported that intramuscular injection of PCEP induces NLRP3, an inflammasome receptor gene, and inflammatory cytokines, including IL-1β and IL-18, in mouse muscle tissue.
444	26344742	Caspase-1 is required for the processing of pro-forms of IL-1β and IL-18 into mature forms and is a critical constituent of the NLRP3 inflammasome.
445	26344742	Hence, in the present study, we investigated the role of caspase-1 in the secretion of IL-1β and IL-18 in PCEP-stimulated splenic dendritic cells (DCs).
446	26344742	Caspase inhibitor YVAD-fmk-treated splenic DCs showed significantly reduced IL-1β and IL-18 secretion in response to PCEP stimulation.
447	26344742	Further, PCEP had no effect on the expression of MHC class II or co-stimulatory molecules, CD86 and CD40, suggesting that PCEP does not induce DC maturation.
448	26344742	Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP.
449	26344742	We have recently reported that intramuscular injection of PCEP induces NLRP3, an inflammasome receptor gene, and inflammatory cytokines, including IL-1β and IL-18, in mouse muscle tissue.
450	26344742	Caspase-1 is required for the processing of pro-forms of IL-1β and IL-18 into mature forms and is a critical constituent of the NLRP3 inflammasome.
451	26344742	Hence, in the present study, we investigated the role of caspase-1 in the secretion of IL-1β and IL-18 in PCEP-stimulated splenic dendritic cells (DCs).
452	26344742	Caspase inhibitor YVAD-fmk-treated splenic DCs showed significantly reduced IL-1β and IL-18 secretion in response to PCEP stimulation.
453	26344742	Further, PCEP had no effect on the expression of MHC class II or co-stimulatory molecules, CD86 and CD40, suggesting that PCEP does not induce DC maturation.
454	24442437	IgA anti-FliC responses were TLR5 and MyD88 dependent and caspase-1 independent.