期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.609060
关键词
nonalcoholic steatohepatitis; G protein-coupled bile acid receptor 1; macrophages; inflammation; NLRP3 inflammasome
类别
资金
- National Nature Science Foundation of China [82071798, 81600450, 81570565, 81971495, 81571564, 91442117, 81870448, 31930020]
- CAMS Innovation Fund for Medical Sciences
- National Science Foundation of Jiangsu Province [BK20191490, BRA2017533]
- Six Talent Peaks Project in Jiangsu Province [2018-WSN-011]
- Jiangsu Science and Technology Association Young Science and Technology Talents Lifting Project [DG000D4007]
- Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials
In NASH, TGR5 expression is decreased, leading to exacerbated liver damage and enhanced inflammatory response in TGR5(-/-) mice. TGR5 deficiency promotes NLRP3 inflammasome activation and M1 macrophage polarization.
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with dysregulation of liver metabolism and inflammation. G-protein coupled bile acid receptor 1 (TGR5) is a cell surface receptor that is involved in multiple metabolic pathways. However, the functions of TGR5 in regulating macrophage innate immune activation in NASH remain unclear. Here, we found that TGR5 expression was decreased in liver tissues from humans and mice with NASH. Compared to wild type (WT) mice, TGR5-knockout (TGR5(-/-)) mice exhibited exacerbated liver damage, increased levels of proinflammatory factors, and enhanced M1 macrophage polarization. Moreover, TGR5 deficiency facilitated M1 macrophage polarization by promoting NLRP3 inflammasome activation and caspase-1 cleavage. Taken together, our findings revealed that TGR5 signaling attenuated liver steatosis and inflammation and inhibited NLRP3-mediated M1 macrophage polarization in NASH.
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