TGR5 ligands as potential therapeutics in inflammatory diseases

Takeda G protein-coupled receptor 5 (TGR5), also known as Gpbar1, membrane-type bile acid receptor (M-BAR), or GPR131 is a G protein-coupled receptor that is best known for its activation by bile acids. TGR5 has been found to regulate a number of specific processes, including energy expenditure and glucagon-like peptide-1 release. Other actions in which TGR5 is implied range from regulating bile acid homeostasis to playing a role in the nervous system. The receptor is increasingly associated with the regulation of inflammatory responses in a number of cells that are relevant to the immune response. TGR5 exerts antiinflammatory actions by decreasing adhesion molecule expression in endothelial cells and inhibiting proinflammatory cytokine production in macrophages. A number of animal models also hint toward the antiinflammatory actions of TGR5. These include models of atherosclerosis, colitis, and inflammation-driven liver diseases. In the current review, we provide a comprehensive overview of TGR5 with a focus on its role in inflammation. We furthermore describe the currently known agonists of TGR5 and discuss some of the recent findings on TGR5 signaling. The potential drawbacks, as well as the encouraging prospects, of TGR5 will be discussed in view of TGR5 as a therapeutic target in diseases with inflammatory facets.