PT  - JOURNAL ARTICLE
AU  - Hernandez-Cuellar, Eduardo
AU  - Tsuchiya, Kohsuke
AU  - Hara, Hideki
AU  - Fang, Rendong
AU  - Sakai, Shunsuke
AU  - Kawamura, Ikuo
AU  - Akira, Shizuo
AU  - Mitsuyama, Masao
TI  - Cutting Edge: Nitric Oxide Inhibits the NLRP3 Inflammasome
AID  - 10.4049/jimmunol.1202479
DP  - 2012 Dec 01
TA  - The Journal of Immunology
PG  - 5113--5117
VI  - 189
IP  - 11
4099  - http://www.jimmunol.org/content/189/11/5113.short
4100  - http://www.jimmunol.org/content/189/11/5113.full
SO  - J. Immunol.2012 Dec 01; 189
AB  - 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.