title: G protein-coupled receptor 43 moderates gut inflammation through cytokine regulation from mononuclear cells.
abstract: 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.
authors.affiliation: *Department of Gastroenterology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan; †Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Masui
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Funaki
authors.forename: Naotaka
authors.initials: N
authors.lastname: Ogasawara
authors.forename: Mari
authors.initials: M
authors.lastname: Mizuno
authors.forename: Akihito
authors.initials: A
authors.lastname: Iida
authors.forename: Shinya
authors.initials: S
authors.lastname: Izawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kondo
authors.forename: Yoshitsugi
authors.initials: Y
authors.lastname: Ito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamura
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yanamoto
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Noda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanabe
authors.forename: Noriko
authors.initials: N
authors.lastname: Okaniwa
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Kunio
authors.initials: K
authors.lastname: Kasugai
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D016264:Dextran Sulfate / Q000633:toxicity; D004760:Enterocolitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005232:Fatty Acids, Volatile / Q000378:metabolism; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*
chemical_list: D016207:Cytokines; D005232:Fatty Acids, Volatile; C506481:Ffar2 protein, mouse; D043562:Receptors, G-Protein-Coupled; D016264:Dextran Sulfate