Serotonin 5-HT7 Receptor Is Critically Involved in Acute and Chronic Inflammation of the Gastrointestinal Tract. Issue 9 (28th July 2014)

• Record Type: Journal Article
• Authors: Guseva, Daria; Holst, Katrin; Kaune, Beate; Meier, Martin; Keubler, Lydia; Glage, Silke; Buettner, Manuela; Bleich, André; Pabst, Oliver; Bachmann, Oliver; Ponimaskin, Evgeni G.
• Is Part Of: Inflammatory bowel diseases. Volume 20:Issue 9(2014)
• Page Start: 1516
• Page End: 1529
• Publication Date: 2014-07-28
• Subjects: 5-HT7 receptor -- dendritic cells -- DSS-induced colitis -- intestinal inflammation -- Crohn's disease; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000000150
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: Intestinal inflammation is often associated with an increased level of serotonin (5-HT), an important gastrointestinal signaling molecule involved in gut homeostasis through stimulation of specific receptors. In this study, we investigated the role of 5-HT7 receptor (5-HT7 R) in the induction and development of intestinal inflammation using a mouse model of acute and chronic colitis and human patients with Crohn's disease (CD). Methods: Acute colitis was induced through administration of dextran sodium sulfate to wild-type, 5-HT7 R–deficient mice and hematopoietic bone marrow chimera. Chronic colitis was induced in interleukin 10–deficient mice. The role of 5-HT7 R in gut inflammation was assessed using agonist/antagonist treatment. We investigated expression and distribution of 5-HT7 R, extent of gut inflammation with magnetic resonance imaging and histological analysis, survival rate, and disease activity index. Finally, biopsies from the large intestine of patients with CD were analyzed. Results: Under basal conditions, 5-HT7 R is expressed both in enteric neurons and CD11c + cells of the large intestine. Expression of 5-HT7 R significantly increased after induction of colitis in mice and in inflamed intestinal regions of patients with CD in CD11c/CD86 double-positive cells. Pharmacological blockade or genetic ablation of 5-HT7 R resulted in increased severity of both acute and chronic dextran sodium sulfate-induced colitis, whereas receptor stimulation showed an anti-inflammatory effect. Analysis of bone marrow chimera indicated importance of 5-HT7 R expressed by hematopoietic cells in intestinal inflammation. Conclusions: The 5-HT7 R expressed on CD11c/CD86-positive myeloid cells modulates the severity of intestinal inflammation in an acute and chronic colitis and thus represents a potential therapeutic target for the treatment of inflammatory disorders such as CD.