@ARTICLE{10.3389/fphar.2015.00287, AUTHOR={Guo, Cong and Qi, Hui and Yu, Yingjie and Zhang, Qiqi and Su, Jia and Yu, Donna and Huang, Wendong and Chen, Wei-Dong and Wang, Yan-Dong}, TITLE={The G-Protein-Coupled Bile Acid Receptor Gpbar1 (TGR5) Inhibits Gastric Inflammation Through Antagonizing NF-κB Signaling Pathway}, JOURNAL={Frontiers in Pharmacology}, VOLUME={6}, YEAR={2015}, URL={https://www.frontiersin.org/articles/10.3389/fphar.2015.00287}, DOI={10.3389/fphar.2015.00287}, ISSN={1663-9812}, ABSTRACT={Gpbar1 (TGR5), a membrane-bound bile acid receptor, is well-known for its roles in regulation of energy homeostasis and glucose metabolism. Here, we show that mice lacking TGR5 were much more susceptible to lipopolysaccharide (LPS)-induced acute gastric inflammation than wild-type (WT) mice and TGR5 is a negative regulator of gastric inflammation through antagonizing NF-κB signaling pathway. We found that the treatment of TGR5 ligands 23(S)-mCDCA and GPBARA (3-(2-Chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethylisoxazole-4-carboxamide) suppressed gene and protein expression mediated by NF-κB signaling. TGR5 overexpression with ligand treatment inhibited gene expression of interferon-inducible protein 10 (IP-10), TNF-α, and chemoattractant protein-1 (MCP-1) induced by LPS. Furthermore, we revealed that TGR5 activation antagonized NF-κB signaling pathway through suppressing its transcription activity, the phosphorylation of IκBα and p65 translocation, which suggests that TGR5 antagonizes gastric inflammation at least in part by inhibiting NF-κB signaling. These findings identify TGR5 as a negative mediator of gastric inflammation that may serve as an attractive therapeutic tool for human gastric inflammation and cancer.} }