实用休克杂志（中英文）2024，Vol.8Issue(3)：156-160,165,6.
中性粒细胞外陷阱通过STING-TBK1-IRF3信号通路参与脓毒症全身炎症反应
Neutrophil extracellular traps participate in the systemic inflammatory response of sepsis via the STING-TBK1-IRF3 signaling pathway
摘要
Abstract
Objective To investigate the potential role of neutrophil extracellular traps(NETs)in the systemic inflammatory response during sepsis via the STING-TBK1-IRF3 signaling pathway.Methods A sepsis model was established in Balb/c mice using cecal ligation and puncture(CLP).The levels of extracellular endogenous DNA were assessed,and the effects of intraperitoneal DNase I injection on the survival of CLP mice were evaluated.The RAW264.7 mouse cell line was treated with NETs in vitro,and the expression of inflammatory factors was quantified using real-time PCR.Activation of the STING-TBK1-IRF3 signaling pathway was assessed through immunofluorescence,Western blot analysis,and siRNA interference.Results In CLP mice,serum levels of endogenous genomic DNA(gDNA),mitochondrial DNA(mtDNA),NETs,and DNase I increased post-surgery.Intraperitoneal injection of DNase I reduced levels of gDNA,mtDNA,and NETs,resulting in de-creased mortality in CLP mice.NETs induced the expression of IFN-β,TNF-α,IL-6,and CCL2 in RAW264.7 cells,which was partially inhibited by pretreatment with DNase I.NETs activated STING,leading to STING interacting with TBK1,resulting in the phosphorylation of TBK1(Ser 172)and IRF3(Ser 396)and the activation of IRF3.Specific siRNA-mediated inhibition of STING re-duced phosphorylation of TBK1 and IRF3 at these sites and decreased the production of inflammatory factors.Conclusions NETs promote the expression of inflammatory factors through the STING-TBK1-IRF3 signaling pathway,thereby contributing to the inflammatory response in sepsis.关键词
脓毒症/细胞外DNA/中性粒细胞外陷阱/干扰素基因刺激因子/全身炎症反应综合征Key words
Sepsis/Extracellular DNA/Neutrophil extracellular traps/STING/Systemic inflammatory response syndrome引用本文复制引用
钟雅婷,郎玥娇..中性粒细胞外陷阱通过STING-TBK1-IRF3信号通路参与脓毒症全身炎症反应[J].实用休克杂志（中英文）,2024,8(3):156-160,165,6.基金项目
广州市科技计划项目,基础与应用基础研究项目(项目编号:202201010986) （项目编号:202201010986）
