GSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14

作     者：Qianjin Liu Lijin Jiao Mao-Sen Ye Zhiyu Ma Jinsong Yu Ling-Yan Su Wei-Yin Zou Lu-Xiu Yang Chang Chen Yong-Gang Yao 

作者机构：Key Laboratory of Genetic Evolution&Animal Modelsand Key Laboratory of Animal Models&Human Disease Mechanisms of Yunnan ProvinceKunming Institute of ZoologyChinese Academy of Sciences650201KunmingYunnanChina Kunming College of Life ScienceUniversity of Chinese Academy of Sciences650204KunmingYunnanChina Key Laboratory of Biomacromolecules(CAS)National Laboratory of BiomacromoleculesCAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of Sciences100101BeijingChina KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences650201KunmingYunnanChina National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)National Resource Center for Non-Human PrimatesKunming Institute of ZoologyChinese Academy of Sciences650201KunmingChina 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2024年第21卷第6期

页      面：561-574页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：Yunnan Fundamental Research Project(202305AH340006) National Natural Science Foundation of China(32201018) Basic Research Program and Key Project of Yunnan Province(202301AW070013 and 202003AD150009) Youth Innovation Promotion Association(2023403) 

主　　题：GSNOR S-nitrosation NLRP3 inflammasome MAPK14 Septic shock Colitis 

摘      要：Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous ***,the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely *** this study,we demonstrated that S-nitrosoglutathione reductase(GSNOR)deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1βexpression levels and interleukin-1β(IL-1β)secretion in response to NLRP3 inflammasome ***,in vivo experiments utilizing Gsnor^(−/−)mice revealed increased disease severity in both lipopolysaccharide(LPS)-induced septic shock and dextran sodium sulfate(DSS)-induced colitis ***,we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in Gsnor^(−/−)Nlrp3^(−/−)double-knockout(DKO)***,GSNOR deficiency increases the S-nitrosation of mitogen-activated protein kinase 14(MAPK14)at the Cys211 residue and augments MAPK14 kinase activity,thereby promoting Nlrp3 and Il-1βtranscription and stimulating NLRP3 inflammasome *** findings suggested that GSNOR is a regulator of the NLRP3 inflammasome and that reducing the level of S-nitrosylated MAPK14 may constitute an effective strategy for alleviating diseases associated with NLRP3-mediated inflammation.