刺
先天免疫系统
炎症
肝损伤
再灌注损伤
免疫学
医学
干扰素基因刺激剂
免疫系统
单核细胞
缺血
生物
药理学
内科学
工程类
航空航天工程
作者
Junzhe Jiao,Yiya Jiang,Yongxiang Qian,Guanjie Liu,Min Xu,Fang Wang,Xiao Sun,Yueqiu Gao,Li Su,Yifeng Shi,Xiaoni Kong
标识
DOI:10.1016/j.ajpath.2022.09.002
摘要
Ischemia/reperfusion (I/R) injury, aggravated by innate immune cell-mediated inflammatory response, is a major problem in liver transplantation. Stimulator of interferon gene (STING) is a crucial regulatory signaling molecule in the DNA-sensing pathway, and its activation can produce strong innate immunity. However, the STING-mediated innate immune pathway in hepatic I/R injury has not been fully elucidated. In this study, we first examined the STING expression changes in the liver tissues of mice after hepatic I/R injury by using quantitative polymerase chain reaction and Western blot assays. We then investigated the role of STING in I/R injury by using a murine hepatic I/R model. STING up-regulation in mouse liver tissues in response to I/R injury and STING deficiency in myeloid cells was found to significantly ameliorate I/R-induced liver injury and inflammatory responses. STING inhibitors were also able to ameliorate hepatic I/R injury. Mechanically, STING may have a protective effect on hepatic I/R injury by the inhibition of hypoxia-inducible factor-1 alpha and enhancement of phosphorylated AMP-activated protein kinase to reduce macrophage activation. These findings show the potential regulatory effects of STING in hepatic I/R and suggest a new method for clinical protection of hepatic I/R injury.
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