Inflammatory Bowel Diseases

Skip Navigation LinksHome > December 2013 - Volume 19 - Issue 13 > G Protein-Coupled Receptor 43 Moderates Gut Inflammation Thr...
Inflammatory Bowel Diseases:
doi: 10.1097/01.MIB.0000435444.14860.ea
Original Basic Science Articles

G Protein-Coupled Receptor 43 Moderates Gut Inflammation Through Cytokine Regulation from Mononuclear Cells

Masui, Ryuta MD*; Sasaki, Makoto MD, PhD*; Funaki, Yasushi MD, PhD*; Ogasawara, Naotaka MD, PhD*; Mizuno, Mari MD, PhD*; Iida, Akihito MD, PhD*; Izawa, Shinya MD*; Kondo, Yoshihiro MD*; Ito, Yoshitsugi MD*; Tamura, Yasuhiro MD*; Yanamoto, Kenichiro MD*; Noda, Hisatsugu MD*; Tanabe, Atsushi MD*; Okaniwa, Noriko MD*; Yamaguchi, Yoshiharu MD*; Iwamoto, Takashi MD, PhD; Kasugai, Kunio MD, PhD*

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Background: Short-chain fatty acids (SCFAs), which are produced by the fermentation of dietary fiber by intestinal microbiota, may positively influence immune responses and protect against gut inflammation. SCFAs bind to G protein-coupled receptor 43 (GPR43). Here, we show that SCFA–GPR43 interactions profoundly affect the gut inflammatory response.

Methods: Colitis was induced by adding dextran sulfate sodium to the drinking water of GPR43 knockout (−/−) and wild-type mice.

Results: Dextran sulfate sodium–treated GPR43−/− mice exhibited weight loss, increased disease activity index (a combined measure of weight loss, rectal bleeding, and stool consistency), decreased hematocrit, and colon shortening, resulting in significantly worse colonic inflammation than in wild-type mice. Tumor necrosis factor alpha and interleukin 17 protein levels in the colonic mucosa of GPR43−/− mice were significantly higher than in wild-type mice. Treatment of wild-type mice with 150 mM acetate in their drinking water markedly improved these disease indices, with an increase in colon length and decrease in the disease activity index; however, it had no effect on GPR43−/− mice. Mononuclear cell production of tumor necrosis factor alpha after lipopolysaccharide stimulation was suppressed by acetate. This effect was inhibited by anti-GPR43 antibody.

Conclusions: SCFA–GPR43 interactions modulate colitis by regulating inflammatory cytokine production in mononuclear cells.

© Crohn's & Colitis Foundation of America, Inc.

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