title: β-Arrestin 2 mediates G protein-coupled receptor 43 signals to nuclear factor-κB.
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.
authors.affiliation: Targeted Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology.
authors.forename: Su Ui
authors.initials: SU
authors.lastname: Lee
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: In
authors.forename: Mi So
authors.initials: MS
authors.lastname: Kwon
authors.forename: Bi-oh
authors.initials: BO
authors.lastname: Park
authors.forename: Minmi
authors.initials: M
authors.lastname: Jo
authors.forename: Mun-Ock
authors.initials: MO
authors.lastname: Kim
authors.forename: Sungchan
authors.initials: S
authors.lastname: Cho
authors.forename: Sangku
authors.initials: S
authors.lastname: Lee
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Lee
authors.forename: Young Shin
authors.initials: YS
authors.lastname: Kwak
authors.forename: Sunhong
authors.initials: S
authors.lastname: Kim
mesh_terms: D019390:Arrestins / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D043562:Receptors, G-Protein-Coupled
chemical_list: D019390:Arrestins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; C000605254:ARRB2 protein, human; C473103:FFAR2 protein, human; D043562:Receptors, G-Protein-Coupled