β-Arrestin 2 mediates G protein-coupled receptor 43 signals to nuclear factor-κB

Biol Pharm Bull. 2013;36(11):1754-9. doi: 10.1248/bpb.b13-00312. Epub 2013 Aug 29.

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 β-arrestin 2 mediates the internalization of GPR43 by agonist. Agonism of GPR43 reduced the phosphorylation and nuclear translocation of nuclear factor-κB (NF-κB), which was relieved by short interfering RNA (siRNA) of β-arrestin 2. Subsequently, mRNA expression of proinflammatory cytokines, interleukin (IL)-6 and IL-1β, was downregulated by activation of GPR43 and knockdown of β-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arrestins / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • NF-kappa B / metabolism*
  • Receptors, Cell Surface / metabolism*
  • beta-Arrestin 2
  • beta-Arrestins

Substances

  • ARRB2 protein, human
  • Arrestins
  • FFA2R protein, human
  • NF-kappa B
  • Receptors, Cell Surface
  • beta-Arrestin 2
  • beta-Arrestins