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Nitric oxide suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock
文献类型：期刊论文
| 作者 | Mao, KR; Chen, SZ; Chen, MK; Ma, YL; Wang, Y; Huang, B; He, ZY; Zeng, Y; Hu, Y; Sun, SH |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2013 |
| 卷号 | 23期号:2页码:201-212 |
| 关键词 | nitric oxide NLRP3 inflammasome septic shock |
| 通讯作者 | Sun, B (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.,changchen@moon.ibp.ac.cn ; gxmeng@sibs.ac.cn ; bsun@sibs.ac.cn |
| 英文摘要 | Inflammasomes are multi-protein complexes that trigger the activation of caspase-1 and the maturation of interleukin-1 beta (IL-1 beta), yet the regulation of these complexes remains poorly characterized. Here we show that nitric oxide (NO) inhibited the NLRP3-mediated ASC pyroptosome formation, caspase-1 activation and IL-1 beta secretion in myeloid cells from both mice and humans. Meanwhile, endogenous NO derived from iNOS (inducible form of NO synthase) also negatively regulated NLRP3 inflammasome activation. Depletion of iNOS resulted in increased accumulation of dysfunctional mitochondria in response to LPS and ATP, which was responsible for the increased IL-1 beta production and caspase-1 activation. iNOS deficiency or pharmacological inhibition of NO production enhanced NLRP3-dependent cytokine production in vivo, thus increasing mortality from LPS-induced sepsis in mice, which was prevented by NLRP3 deficiency. Our results thus identify NO as a critical negative regulator of the NLRP3 inflammasome via the stabilization of mitochondria. This study has important implications for the design of new strategies to control NLRP3-related diseases. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | NALP3 INFLAMMASOME ; IMMUNE-RESPONSES ; MESSENGER-RNA ; HOST-DEFENSE ; SYNTHASE ; MICE ; EXPRESSION ; DISEASE ; CELLS ; NITROSYLATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000315426400009 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/340]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Mao, KR,Chen, SZ,Chen, MK,et al. Nitric oxide suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock[J]. CELL RESEARCH,2013,23(2):201-212. |
| APA | Mao, KR.,Chen, SZ.,Chen, MK.,Ma, YL.,Wang, Y.,...&Sun, B.(2013).Nitric oxide suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock.CELL RESEARCH,23(2),201-212. |
| MLA | Mao, KR,et al."Nitric oxide suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock".CELL RESEARCH 23.2(2013):201-212. |
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