Genomes and Genes
Summary: A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.
- Koo J, Hong H, Dearth A, Kobayashi K, Koh Y. Intracellular invasion of Orientia tsutsugamushi activates inflammasome in asc-dependent manner. PLoS ONE. 2012;7:e39042 pubmed publisher..Therefore, live O. tsutsugamushi triggers ASC inflammasome activation leading to IL-1? production, which is a critical innate immune response for effective host defense. ..
- Liu Z, Zaki M, Vogel P, Gurung P, Finlay B, Deng W, et al. Role of inflammasomes in host defense against Citrobacter rodentium infection. J Biol Chem. 2012;287:16955-64 pubmed publisher..Thus, production of IL-1? and IL-18 downstream of the Nlrp3 and Nlrc4 inflammasomes plays a critical role in host defense against enteric infections caused by C. rodentium...
- Ge J, Gong Y, Xu Y, Shao F. Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking. Proc Natl Acad Sci U S A. 2012;109:6193-8 pubmed publisher..Our data together suggest a possible link, mediated by the function of SdhA, between LCV trafficking/maturation and suppression of host innate immune detection...
- Franchi L, Kamada N, Nakamura Y, Burberry A, Kuffa P, Suzuki S, et al. NLRC4-driven production of IL-1? discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat Immunol. 2012;13:449-56 pubmed publisher..Thus, NLRC4-dependent production of IL-1? by intestinal phagocytes represents a specific response that discriminates pathogenic bacteria from commensal bacteria and contributes to host defense in the intestine. ..
- Akhter A, Caution K, Abu Khweek A, Tazi M, Abdulrahman B, Abdelaziz D, et al. Caspase-11 promotes the fusion of phagosomes harboring pathogenic bacteria with lysosomes by modulating actin polymerization. Immunity. 2012;37:35-47 pubmed publisher..However, caspase-11 was dispensable for the fusion of lysosomes with phagosomes containing nonpathogenic bacteria, uncovering a fundamental difference in the trafficking of phagosomes according to their cargo. ..
- Ayna G, Krysko D, Kaczmarek A, Petrovski G, Vandenabeele P, Fesus L. ATP release from dying autophagic cells and their phagocytosis are crucial for inflammasome activation in macrophages. PLoS ONE. 2012;7:e40069 pubmed publisher..These findings demonstrate that NALP3 performs key upstream functions in inflammasome activation in mouse macrophages engulfing dying autophagic cells, and that these functions lead to pro-inflammatory responses. ..
- Usui F, Shirasuna K, Kimura H, Tatsumi K, Kawashima A, Karasawa T, et al. Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice. Biochem Biophys Res Commun. 2012;425:162-8 pubmed publisher..Our findings suggest that caspase-1 plays a critical role in vascular inflammation and atherosclerosis, and that modulation of caspase-1 could be a potential target for prevention and treatment of atherosclerosis. ..
- Qu Y, Misaghi S, Izrael Tomasevic A, Newton K, Gilmour L, Lamkanfi M, et al. Phosphorylation of NLRC4 is critical for inflammasome activation. Nature. 2012;490:539-42 pubmed publisher..typhimurium infection, so phosphorylation of NLRC4 S533 probably drives conformational changes necessary for NLRC4 inflammasome activity and host innate immunity. ..
- Maslanik T, Mahaffey L, Tannura K, Beninson L, Greenwood B, Fleshner M. The inflammasome and danger associated molecular patterns (DAMPs) are implicated in cytokine and chemokine responses following stressor exposure. Brain Behav Immun. 2013;28:54-62 pubmed publisher..The results increase our mechanistic understanding of systemic sterile inflammatory responses, and provide novel evidence that the inflammasome may be an important pharmacological target for treatment of these conditions. ..
- Shenoy A, Wellington D, Kumar P, Kassa H, Booth C, Cresswell P, et al. GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals. Science. 2012;336:481-5 pubmed publisher..Thus, GBP5 serves as a unique rheostat for NLRP3 inflammasome activation and extends our understanding of the inflammasome complex beyond its core machinery. ..
- Masters S, Gerlic M, Metcalf D, Preston S, Pellegrini M, O Donnell J, et al. NLRP1 inflammasome activation induces pyroptosis of hematopoietic progenitor cells. Immunity. 2012;37:1009-23 pubmed publisher..Conversely, NLRP1-deficient mice showed enhanced recovery from chemotherapy and LCMV infection, demonstrating that NLRP1 acts as a cellular sentinel to alert Caspase-1 to hematopoietic and infectious stress. ..
- Lima Júnior D, Costa D, Carregaro V, Cunha L, Silva A, Mineo T, et al. Inflammasome-derived IL-1? production induces nitric oxide-mediated resistance to Leishmania. Nat Med. 2013;19:909-15 pubmed publisher..In this manuscript we identify a major signaling platform for host resistance to Leishmania spp. infection and describe the molecular mechanisms underlying Leishmania-induced NO production. ..
- Vajjhala P, Mirams R, Hill J. Multiple binding sites on the pyrin domain of ASC protein allow self-association and interaction with NLRP3 protein. J Biol Chem. 2012;287:41732-43 pubmed publisher..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. ..
- Rajamäki K, Nordström T, Nurmi K, Akerman K, Kovanen P, Öörni K, et al. Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3 inflammasome. J Biol Chem. 2013;288:13410-9 pubmed publisher..Low pH may thus contribute to inflammation in acidosis-associated pathologies such as atherosclerosis and post-ischemic inflammatory responses. ..
- von Moltke J, Trinidad N, Moayeri M, Kintzer A, Wang S, Van Rooijen N, et al. Rapid induction of inflammatory lipid mediators by the inflammasome in vivo. Nature. 2012;490:107-11 pubmed publisher..Our results therefore identify eicosanoids as a previously unrecognized cell-type-specific signalling output of the inflammasome with marked physiological consequences in vivo. ..
- Gomes M, Campos P, Oliveira F, Corsetti P, Bortoluci K, Cunha L, et al. Critical role of ASC inflammasomes and bacterial type IV secretion system in caspase-1 activation and host innate resistance to Brucella abortus infection. J Immunol. 2013;190:3629-38 pubmed publisher..Taken together, our results indicate that Brucella is sensed by ASC inflammasomes that collectively orchestrate a robust caspase-1 activation and proinflammatory response. ..
- Dixon L, Flask C, Papouchado B, Feldstein A, Nagy L. Caspase-1 as a central regulator of high fat diet-induced non-alcoholic steatohepatitis. PLoS ONE. 2013;8:e56100 pubmed publisher..Our aims were to examine the role of caspase-1 in high fat-induced NASH. C57BL/6 wild-type and caspase 1-knockout (Casp1(-/-)) mice were placed on a 12-week high fat diet...
- Savaryn J, Reitsma J, Bigley T, Halligan B, Qian Z, Yu D, et al. Human cytomegalovirus pUL29/28 and pUL38 repression of p53-regulated p21CIP1 and caspase 1 promoters during infection. J Virol. 2013;87:2463-74 pubmed publisher..During infection, pUL29/28 and pUL38 contributed to the inhibition of p21CIP1 as well as caspase 1 expression. The expression of several other p53-regulating genes was not altered...
- Py B, Kim M, Vakifahmetoglu Norberg H, Yuan J. Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome activity. Mol Cell. 2013;49:331-8 pubmed publisher..Our results elucidate a regulatory mechanism involving BRCC3-dependent NLRP3 regulation and highlight NLRP3 ubiquitination as a potential therapeutic target for inflammatory diseases. ..
- Jacobson L, Lima H, Goldberg M, Gocheva V, Tsiperson V, Sutterwala F, et al. Cathepsin-mediated necrosis controls the adaptive immune response by Th2 (T helper type 2)-associated adjuvants. J Biol Chem. 2013;288:7481-91 pubmed publisher..Together our findings suggest that necrotic cell death is a powerful mediator of a Th2-associated immune response...
- Zheng Y, Humphry M, Maguire J, Bennett M, Clarke M. Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1?, controlling necrosis-induced sterile inflammation. Immunity. 2013;38:285-95 pubmed publisher..Thus, we report a cell type-dependent process that fundamentally governs IL-1? activity postnecrosis and the mechanism allowing conditional release of this blockade. ..
- Yang E, Kim S, Kim J, Choi I. Inflammasome formation and IL-1? release by human blood monocytes in response to silver nanoparticles. Biomaterials. 2012;33:6858-67 pubmed publisher..Moreover, these findings also suggest that the immunological significance of silver nanoparticles should be considered with respect to their capacity to synergistically activate immune responses...
- Denes A, Lopez Castejon G, Brough D. Caspase-1: is IL-1 just the tip of the ICEberg?. Cell Death Dis. 2012;3:e338 pubmed publisher..We attempt here to summarise the evidence for caspase-1 as a cell death enzyme and propose that, in addition to the processing of IL-1?, caspase-1 has an important and a conserved role as a cell death protease. ..
- Saiga H, Kitada S, Shimada Y, Kamiyama N, Okuyama M, Makino M, et al. Critical role of AIM2 in Mycobacterium tuberculosis infection. Int Immunol. 2012;24:637-44 pubmed..Mtb DNA, which was present in the cytosol, co-localized with AIM2. Taken together, these findings demonstrate that AIM2 plays an important role in M. tuberculosis infection through the recognition of Mtb DNA. ..
- Sagulenko V, Thygesen S, Sester D, Idris A, Cridland J, Vajjhala P, et al. AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC. Cell Death Differ. 2013;20:1149-60 pubmed publisher..Thus caspase-8 is an integral part of the inflammasome, and this extends the relevance of the inflammasome to cell types that do not express caspase-1. ..
- Pierini R, Juruj C, Perret M, Jones C, Mangeot P, Weiss D, et al. AIM2/ASC triggers caspase-8-dependent apoptosis in Francisella-infected caspase-1-deficient macrophages. Cell Death Differ. 2012;19:1709-21 pubmed publisher..This work underscores the crosstalk between inflammasome components and the apoptotic machinery and highlights the versatility of the pathway, which can switch from pyroptosis to apoptosis. ..
- Frew B, Joag V, Mogridge J. Proteolytic processing of Nlrp1b is required for inflammasome activity. PLoS Pathog. 2012;8:e1002659 pubmed publisher..Our work indicates that a post-translational modification enables Nlrp1b to function. ..
- Jung C, Meinzer U, Montcuquet N, Thachil E, Chateau D, Thiébaut R, et al. Yersinia pseudotuberculosis disrupts intestinal barrier integrity through hematopoietic TLR-2 signaling. J Clin Invest. 2012;122:2239-51 pubmed publisher..Therefore, Y. pseudotuberculosis subverts intestinal barrier function by altering the interplay between immune and epithelial cells during infection. ..
- Menzel C, Sun Q, Loughran P, Pape H, Billiar T, Scott M. Caspase-1 is hepatoprotective during trauma and hemorrhagic shock by reducing liver injury and inflammation. Mol Med. 2011;17:1031-8 pubmed publisher..These findings may have implications for the treatment of trauma patients and may lead to progress in prevention or treatment of multiple organ failure (MOF). ..
- Abdelaziz D, Gavrilin M, Akhter A, Caution K, Kotrange S, Khweek A, et al. Apoptosis-associated speck-like protein (ASC) controls Legionella pneumophila infection in human monocytes. J Biol Chem. 2011;286:3203-8 pubmed publisher..pneumophila manipulates ASC levels to evade inflammasome activation and grow in human monocytes. By targeting ASC, L. pneumophila modulates the inflammasome, the apoptosome, and NF-?B pathway simultaneously. ..
- Bae J, Park H. Crystal structure of NALP3 protein pyrin domain (PYD) and its implications in inflammasome assembly. J Biol Chem. 2011;286:39528-36 pubmed publisher..The most interesting aspect of the structure was the unexpected disulfide bond between Cys-8 and Cys-108, which might be important for regulation of the activity of NALP3 by redox potential...
- Fettelschoss A, Kistowska M, LeibundGut Landmann S, Beer H, Johansen P, Senti G, et al. Inflammasome activation and IL-1? target IL-1? for secretion as opposed to surface expression. Proc Natl Acad Sci U S A. 2011;108:18055-60 pubmed publisher..We further demonstrate that IL-1? directly binds IL-1?, thus identifying IL-1? as a shuttle for another proinflammatory cytokine. These results have direct impact on selective treatment modalities of inflammatory diseases. ..
- Brodsky I, Medzhitov R. Pyroptosis: macrophage suicide exposes hidden invaders. Curr Biol. 2011;21:R72-5 pubmed publisher..A new study now highlights the specific importance of pyroptosis in resistance to intracellular pathogens. ..
- Meissner F, Seger R, Moshous D, Fischer A, Reichenbach J, Zychlinsky A. Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease. Blood. 2010;116:1570-3 pubmed publisher..Our results identify phagocyte oxidase defective monocytes as a source of elevated IL-1 and provide a potential therapeutic option to ameliorate inflammatory conditions associated with CGD. ..
- Abdul Sater A, SaÃ¯d Sadier N, Padilla E, Ojcius D. Chlamydial infection of monocytes stimulates IL-1beta secretion through activation of the NLRP3 inflammasome. Microbes Infect. 2010;12:652-661 pubmed publisher..Use of inhibitors that target the inflammasome in animals should therefore dampen inflammation during chlamydial infection. ..
- Lamkanfi M. Emerging inflammasome effector mechanisms. Nat Rev Immunol. 2011;11:213-20 pubmed publisherb>Caspase 1 activation by inflammasome complexes in response to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) induces the maturation and secretion of the pro-inflammatory cytokines ..
- Mulla M, Myrtolli K, Potter J, Boeras C, Kavathas P, Sfakianaki A, et al. Uric acid induces trophoblast IL-1? production via the inflammasome: implications for the pathogenesis of preeclampsia. Am J Reprod Immunol. 2011;65:542-8 pubmed publisher..This may provide a novel mechanism for the induction of inflammation at the maternal–fetal interface leading to placental dysfunction and adverse pregnancy outcome, including preeclampsia. ..
- Reisetter A, Stebounova L, Baltrusaitis J, Powers L, Gupta A, Grassian V, et al. Induction of inflammasome-dependent pyroptosis by carbon black nanoparticles. J Biol Chem. 2011;286:21844-52 pubmed publisher..of macrophages to carbon black nanoparticles resulted in inflammasome activation as defined by cleavage of caspase 1 to its active form and downstream IL-1? release...
- Zheng Y, Lilo S, Brodsky I, Zhang Y, Medzhitov R, Marcu K, et al. A Yersinia effector with enhanced inhibitory activity on the NF-?B pathway activates the NLRP3/ASC/caspase-1 inflammasome in macrophages. PLoS Pathog. 2011;7:e1002026 pubmed publisher..This pro-inflammatory form of apoptosis may represent an early innate immune response to highly virulent pathogens such as Y. pestis KIM that have evolved an enhanced ability to inhibit host signaling pathways. ..
- Anders H, Muruve D. The inflammasomes in kidney disease. J Am Soc Nephrol. 2011;22:1007-18 pubmed publisher..We further provide a perspective on the potential roles of the inflammasomes in the pathogenesis of acute and chronic kidney diseases. ..
- Stienstra R, van Diepen J, Tack C, Zaki M, van de Veerdonk F, Perera D, et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc Natl Acad Sci U S A. 2011;108:15324-9 pubmed publisher..These findings reveal a critical function of the inflammasome in obesity and insulin resistance, and suggest inhibition of the inflammasome as a potential therapeutic strategy. ..
- Toma C, Higa N, Koizumi Y, Nakasone N, Ogura Y, McCoy A, et al. Pathogenic Vibrio activate NLRP3 inflammasome via cytotoxins and TLR/nucleotide-binding oligomerization domain-mediated NF-kappa B signaling. J Immunol. 2010;184:5287-97 pubmed publisher..Our results identify the NLRP3 inflammasome as a sensor of Vibrio infections through the action of bacterial cytotoxins and differential activation of innate signaling pathways acting upstream of NF-kappaB. ..
- Eltom S, Stevenson C, Rastrick J, Dale N, Raemdonck K, Wong S, et al. P2X7 receptor and caspase 1 activation are central to airway inflammation observed after exposure to tobacco smoke. PLoS ONE. 2011;6:e24097 pubmed publisher..The aim of this study was to determine whether activation of the P2X7/caspase 1 pathway has a functional role in CS-induced airway inflammation...
- Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, et al. Non-canonical inflammasome activation targets caspase-11. Nature. 2011;479:117-21 pubmed publisher..These data highlight a unique pro-inflammatory role for caspase-11 in the innate immune response to clinically significant bacterial infections. ..
- Kaushik D, Gupta M, Kumawat K, Basu A. NLRP3 inflammasome: key mediator of neuroinflammation in murine Japanese encephalitis. PLoS ONE. 2012;7:e32270 pubmed publisher..Our results identify a mechanism mediated by Reactive Oxygen Species (ROS) production and potassium efflux as the two danger signals that link JEV infection to caspase-1 activation resulting in subsequent IL-1? and IL-18 maturation. ..
- Miao E, Leaf I, Treuting P, Mao D, Dors M, Sarkar A, et al. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol. 2010;11:1136-42 pubmed publisher..This demonstrates that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1? and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system...
- Shigeoka A, Mueller J, Kambo A, Mathison J, King A, Hall W, et al. An inflammasome-independent role for epithelial-expressed Nlrp3 in renal ischemia-reperfusion injury. J Immunol. 2010;185:6277-85 pubmed publisher..recruits apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc), and triggers caspase 1 activation and the maturation of proinflammatory cytokines such as IL-1? and IL-18...