Inflammasomes are multi-protein complexes that trigger the maturation of the pro-inflammatory cytokines IL-1β and IL-18 by activating caspase-1. NLRP3 inflammasome is the most studied inflammasome that responds not only to pathogens but also to a variety of ’danger signals’ released in inflamed tissues. Recently, a new study by researchers from Chinese Academy of Sciences provide new insight into the negative regulation of NLRP3 inflammasome.
Under the supervision of Prof. SUN Bing from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Dr. MAO Kairui and CHEN Shuzhen found that nitric oxide(NO) could inhibit the NLRP3 inflammasome activation including ASC pyroptosome formation, caspase-1 activation and IL-1β secretion in response to LPS and ATP, nigericin or MSU crystals. In vivo, iNOS deficiency or pharmacological inhibition of NO production enhanced NLRP3-dependent cytokines production, thus increasing mortality from LPS-induced sepsis in mice, which was prevented by NLRP3 deficiency.
The researchers proposed that depletion of iNOS resulted in increased accumulation of dysfunctional mitochondria in response to LPS and ATP, which was responsible for the increased IL-1β production and caspase-1 activation. This study has important implications for the design of new strategies to control NLRP3-related diseases.
This work entitled "Nitric oxide suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock" was published in Cell Research on January 16th, 2013.
This work was supported by grants from Ministry of Science and Technology of China and National Natural Science Foundation of China.
AUTHOR CONTACT:
Dr. SUN Bing
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
Tel:021- 54921375
Email: bsun@sibs.ac.cn
NOS inhibition and iNOS deficiency increase susceptibility to LPS-induced death. (Image provided by Dr. SUN Bing)
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