G protein-coupled receptor 39 plays an anti-inflammatory role by enhancing IL-10 production from macrophages under inflammatory conditions

The possible role of G protein-coupled receptor 39 (GPR39) in inflammation was examined in macrophages. Gpr39 expression increased in thioglycollate-induced peritoneal macrophages. TC-G 1008, a G protein-coupled receptor 39 agonist, enhanced interleukin (IL)-10 production from thioglycollate-induced peritoneal macrophages stimulated with lipopolysaccharide (LPS) in vitro. In addition, the oral administration of TC-G 1008 enhanced serum IL-10 concentrations in an LPS-induced murine model of sepsis. The ablation of G protein-coupled receptor 39 significantly reduced IL-10 production by TC-G 1008 in thioglycollate-induced peritoneal macrophages stimulated with LPS and in the LPS-induced murine model of sepsis. Moreover, the oral administration of TC-G 1008 significantly improved the survival rate in the LPS-induced murine model of sepsis. Taken together, our data suggest that G protein-coupled receptor 39 exhibits an anti-inflammatory activity by enhancing IL-10 production from macrophages.