beta-Arrestin 2 Mediates G Protein-Coupled Receptor 43 Signals to Nuclear Factor-kappa B

Abstract

G-protein coupled receptor 43 (GPR43) serves as a receptor for short-chain fatty acids (SCFAs), implicated in neutrophil migration and inflammatory cytokine production. However, the intracellular signaling pathway mediating GPR43 signaling remains unclear. Here, we show that beta-arrestin 2 mediates the internalization of GPR43 by agonist. Agonisrn of GPR43 reduced the phosphorylation and nuclear translocation of nuclear factor-kappa B (NF-kappa B), which was relieved by short interfering RNA (siRNA) of beta-arrestin 2. Subsequently, mRNA expression of proinflammatory cytokines, interleukin (IL)-6 and IL-1 beta, was downregulated by activation of GPR43 and knockdown of beta-arrestin 2 recovered the expression of the cytokines. Taken together, these results suggest that GPR43 may be a plausible target for a variety of inflammatory diseases.