TLR9型
败血症
基因敲除
免疫学
癌症研究
生物
化学
医学
基因表达
细胞凋亡
生物化学
基因
DNA甲基化
作者
Lili Li,Lili Jiang,Shengjun Mao,Jiajian Ye
标识
DOI:10.1615/critrevimmunol.2023050273
摘要
Sepsis is a life-threatening organ dysfunction due to dysregulated host response to infection, accompanied by a high rate of mortality worldwide. During sepsis progression, toll-like receptors (TLRs) play essential roles in the aberrant inflammatory response that contributes to sepsis-related mortality. Here, we demonstrated a critical role of TLR9 in the progression of sepsis. A septic mouse model was established by cecal ligation and puncture (CLP), then administered with lentivirus encoding si-TLR9/LY294002. TLR9 protein expression and p65 nuclear translocation level/TLR9 protein positive expression/interaction between TLR9 and MyD88 in the intestinal tissues were examined by Western blot/immunohistochemistry/Co-IP assays. Serum levels of pro-inflammatory factors (IL-6, TNF-α) as well as bacterial contents in the liver/spleen/mesenteric lymph nodes (MLN) were measured by ELISA and bacterial mobility assay. TLR9 expression was augmented in the intestinal tissues, TLR9 and MyD88 interaction was enhanced, nuclear p65 protein level was increased, cytoplasmic p65 protein level was decreased, and the MyD88/NF-κB pathway was activated in CLP-induced septic mice, while TLR9 knockout protected against CLP-induced sepsis via the MyD88/NF-κB pathway inactivation. Briefly, TLR9 inhibition-mediated protection against CLP-induced sepsis was associated with a reduction in pro-inflammatory cytokine release and a promotion of bacterial clearance via a mechanism involving the MyD88/NF-κB pathway inactivation.
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