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Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis.
Singh, Nagendra; Gurav, Ashish; Sivaprakasam, Sathish; Brady, Evan; Padia, Ravi; Shi, Huidong; Thangaraju, Muthusamy; Prasad, Puttur D; Manicassamy, Santhakumar; Munn, David H; Lee, Jeffrey R; Offermanns, Stefan; Ganapathy, Vadivel.
Afiliação
  • Singh N; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: nasingh@gru.edu.
  • Gurav A; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
  • Sivaprakasam S; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
  • Brady E; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
  • Padia R; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
  • Shi H; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA.
  • Thangaraju M; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA.
  • Prasad PD; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA.
  • Manicassamy S; Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA.
  • Munn DH; Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA; Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
  • Lee JR; Department of Pathology, Charlie Norwood Veterans Administration Medical Center, Augusta, GA 30904, USA.
  • Offermanns S; Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
  • Ganapathy V; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: vganapat@gru.edu.
Immunity ; 40(1): 128-39, 2014 Jan 16.
Article em En | MEDLINE | ID: mdl-24412617
ABSTRACT
Commensal gut microflora and dietary fiber protect against colonic inflammation and colon cancer through unknown targets. Butyrate, a bacterial product from fermentation of dietary fiber in the colon, has been implicated in this process. GPR109A (encoded by Niacr1) is a receptor for butyrate in the colon. GPR109A is also a receptor for niacin, which is also produced by gut microbiota and suppresses intestinal inflammation. Here we showed that Gpr109a signaling promoted anti-inflammatory properties in colonic macrophages and dendritic cells and enabled them to induce differentiation of Treg cells and IL-10-producing T cells. Moreover, Gpr109a was essential for butyrate-mediated induction of IL-18 in colonic epithelium. Consequently, Niacr1(-/-) mice were susceptible to development of colonic inflammation and colon cancer. Niacin, a pharmacological Gpr109a agonist, suppressed colitis and colon cancer in a Gpr109a-dependent manner. Thus, Gpr10a has an essential role in mediating the beneficial effects of gut microbiota and dietary fiber in colon.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Nicotínicos / Colite / Colo / Neoplasias do Colo / Receptores Acoplados a Proteínas G / Células Epiteliais / Carcinogênese Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Nicotínicos / Colite / Colo / Neoplasias do Colo / Receptores Acoplados a Proteínas G / Células Epiteliais / Carcinogênese Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article