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The Proton-activatedReceptor GPR4Modulates IntestinalInflammation Yu WangCheryl de VallièrePedro Henrique Imenez Silva2017 год

The Proton-activated Receptor GPR4 Modulates Intestinal Inflammation
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Аннотация: During active inflammation, intraluminal intestinal pH is decreased in patients with inflammatory bowel disease [IBD]. Acidic pH may play a role in IBD pathophysiology. Recently, proton-sensing G-protein coupled receptors were identified, including GPR4, OGR1 [GPR68], and TDAG8 [GPR65]. We investigated whether GPR4 is involved in intestinal inflammation.The role of GPR4 was assessed in murine colitis models by chronic dextran sulphate sodium [DSS] administration and by cross-breeding into an IL-10 deficient background for development of spontaneous colitis. Colitis severity was assessed by body weight, colonoscopy, colon length, histological score, cytokine mRNA expression, and myeloperoxidase [MPO] activity. In the spontaneous Il-10-/- colitis model, the incidence of rectal prolapse and characteristics of lamina propria leukocytes [LPLs] were analysed.Gpr4-/- mice showed reduced body weight loss and histology score after induction of chronic DSS colitis. In Gpr4-/-/Il-10-/- double knock-outs, the onset and progression of rectal prolapse were significantly delayed and mitigated compared with Gpr4+/+/Il-10-/- mice. Double knock-out mice showed lower histology scores, MPO activity, CD4+ T helper cell infiltration, IFN-γ, iNOS, MCP-1 [CCL2], CXCL1, and CXCL2 expression compared with controls. In colon, GPR4 mRNA was detected in endothelial cells, some smooth muscle cells, and some macrophages.Absence of GPR4 ameliorates colitis in IBD animal models, indicating an important regulatory role in mucosal inflammation, thus providing a new link between tissue pH and the immune system. Therapeutic inhibition of GPR4 may be beneficial for the treatment of IBD.
Год издания: 2017
Авторы: Yu Wang, Cheryl de Vallière, Pedro Henrique Imenez Silva, Irina Leonardi, Sven Gruber, Alexandra Gerstgrasser, Hassan Melhem, Achim Weber, Katharina Leucht, Lutz Wolfram, Martin Hausmann, Carsten Krieg, Koray Thomasson, Onur Boyman, Isabelle Frey‐Wagner, Gerhard Rogler, Carsten A. Wagner
Издательство: Oxford University Press
Источник: Journal of Crohn s and Colitis
Ключевые слова: Gastroesophageal reflux and treatments, Helicobacter pylori-related gastroenterology studies, Ion Transport and Channel Regulation
Другие ссылки: Journal of Crohn s and Colitis (PDF)
Journal of Crohn s and Colitis (HTML)
Zurich Open Repository and Archive (University of Zurich) (HTML)
PubMed (HTML)