刺
对乙酰氨基酚
药理学
体内
肝损伤
化学
细胞凋亡
炎症
外周血单个核细胞
先天免疫系统
体外
免疫学
生物化学
医学
生物
受体
工程类
航空航天工程
生物技术
作者
Congyang Zheng,Yuanyuan Chen,Tingting He,Xiu Ye,Dong Xu,Xianling Wang,Xinru Wen,Chengwei Li,Qing Yao,Simin Chen,Xiaoyan Zhan,Lili Gao,Zhaofang Bai
标识
DOI:10.1186/s10020-024-00924-6
摘要
Abstract Background The cGAS-STING pathway is an important component of the innate immune system and plays significant role in acetaminophen-induced liver injury (AILI). Pentagalloylglucose (PGG) is a natural polyphenolic compound with various beneficial effects, including anti-cancer, antioxidant, anti-inflammatory, and liver-protective properties; however, whether it can be used for the treatment of AILI and the specific mechanism remain unclear. Materials and methods A cell culture model was created to study the effect of PGG on cGAS-STING pathway activation using various techniques including western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and immunoprecipitation (IP). The effect of PGG was investigated in vivo by establishing a dimethylxanthenone acetic acid (DMXAA)-mediated activation model. An AILI model was used to evaluate the hepatoprotective and therapeutic effects of PGG by detecting liver function indicators, liver histopathology, and cGAS-STING pathway-related indicators in mice with AILI. Results PGG blocked cGAS-STING pathway activation in bone marrow-derived macrophages (BMDMs), THP-1 cells, and peripheral blood mononuclear cells (PBMCs) in vitro. Furthermore, PGG inhibited the generation of type I interferons (IFN-I) and the secretion of inflammatory factors in DMXAA-induced in vivo experiments. In addition, PGG also reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), improved liver tissue damage and apoptosis, and inhibited the cGAS-STING pathway activation caused by acetaminophen. In terms of the mechanism, PGG disrupted the connection between STING and TBK1. Conclusions PGG exerts a protective effect against AILI by blocking the cGAS-STING pathway, offering a promising treatment strategy.
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