STING mediates microglial pyroptosis via interaction with NLRP3 in cerebral ischaemic stroke

作     者：Wenyu Li Nan Shen Lingqi Kong Hongmei Huang Xinyue Wang Yan Zhang Guoping Wang Pengfei Xu Wei Hu 

作者机构：Department of NeurologyThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina 

出 版 物：《Stroke & Vascular Neurology》 (卒中与血管神经病学（英文）)

年 卷 期：2024年第9卷第2期

页      面：153-164页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.82101368) the Anhui Provincial Natural Science Foundation(Nos.2008085QH368 and 2108085MH272) 

主　　题：NLRP3 cerebral inflammation 

摘      要：background Ischaemia-evoked neuroinflammation is a critical pathogenic event following ischaemic *** D(GSDMD)-associated pyroptosis represents a type of inflammation-associated programmed cell death,which can exacerbate neuroinflammatory responses and brain *** of interferon genes(STING)was recently described as a vital innate immune adaptor protein associated with ***,the regulatory effects of STING on microglial pyroptosis post-stroke have not been well *** STING-knockout and wild-type(WT)mice were subjected to middle cerebral artery occlusion(MCAO).STING small interfering RNA(siRNA)was transfected into BV2 cells before oxygen-glucose deprivation/reoxygenation(OGD/R).STING-overexpressing adeno-associated virus(AAV)and NOD-like receptor family pyrin domain containing 3(NLRP3)siRNA were administered by stereotaxic injection.2,3,5-Triphenyl tetrazolium chloride(TTC)staining,TdT-mediated dUTP nick end labeling(TUNEL)staining,Fluoro-Jade C(FJC)staining,neurobehavioural tests,immunohistochemistry,cytokine antibody array assay,transmission electron microscopy,immunoblot,Enzyme-linked immunosorbent assay(ELISA)and quantitative real-time polymerase chain reaction(qRT-PCR)were carried ***-immunoprecipitation assays were used to investigate the interplay between STING and *** STING expression was increased after MCAO and mainly detected on *** deletion alleviated brain infarction,neuronal damage and neurobehavioural impairment in mice subjected to *** knockout suppressed microglial activation and the secretion of inflammatory chemokines,accompanied by mitigation of microglial *** upregulation of microglial STING by AAV-F4/80-STING aggravated brain injury and microglial ***,co-immunoprecipitation showed that STING bound to NLRP3 in *** of NLRP3 siRNA reversed AAV-F4/80-STING-induced deterioration of microglial pyropt