Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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β-Arrestin 2 Mediates G Protein-Coupled Receptor 43 Signals to Nuclear Factor-κB
Su Ui LeeHyun Ju InMi So KwonBi-oh ParkMinmi JoMun-Ock KimSungchan ChoSangku LeeHyun-Jun LeeYoung Shin KwakSunhong Kim
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2013 Volume 36 Issue 11 Pages 1754-1759

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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.

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© 2013 The Pharmaceutical Society of Japan
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