title: Cutting edge: nitric oxide inhibits the NLRP3 inflammasome.
abstract: Although the NLRP3 inflammasome plays a pivotal role in host defense, its uncontrolled activation is associated with inflammatory disorders, suggesting that regulation of the inflammasome is important to prevent detrimental effects. Type I IFNs and long-term LPS stimulation were shown to negatively regulate NLRP3 activation. In this study, we found that endogenous NO is involved in the regulation of NLRP3 inflammasome activation by either IFN-β pretreatment or long-term LPS stimulation. Furthermore, S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, markedly inhibited NLRP3 inflammasome activation, whereas the AIM2 and NLRC4 inflammasomes were only partially inhibited by SNAP. An increase in mitochondrial reactive oxygen species induced by ATP was only modestly affected by SNAP treatment. Interestingly, S-nitrosylation of NLRP3 was detected in macrophages treated with SNAP, and this modification may account for the NO-mediated mechanism controlling inflammasome activation. Taken together, these results revealed a novel role for NO in regulating the NLRP3 inflammasome.
authors.affiliation: Department of Microbiology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Hernandez-Cuellar
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Hideki
authors.initials: H
authors.lastname: Hara
authors.forename: Rendong
authors.initials: R
authors.lastname: Fang
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Sakai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kawamura
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Masao
authors.initials: M
authors.lastname: Mitsuyama
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D058847:Inflammasomes / Q000187:drug effects* / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009569:Nitric Oxide / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: C540422:Aim2 protein, mouse; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D058847:Inflammasomes; C512299:Ipaf protein, mouse; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D016899:Interferon-beta; D026423:S-Nitroso-N-Acetylpenicillamine; D000255:Adenosine Triphosphate