title: Serotonin 5-HT7 receptor is critically involved in acute and chronic inflammation of the gastrointestinal tract.
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-HT7R) 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-HT7R-deficient mice and hematopoietic bone marrow chimera. Chronic colitis was induced in interleukin 10-deficient mice. The role of 5-HT7R in gut inflammation was assessed using agonist/antagonist treatment. We investigated expression and distribution of 5-HT7R, 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-HT7R is expressed both in enteric neurons and CD11c cells of the large intestine. Expression of 5-HT7R 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-HT7R 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-HT7R expressed by hematopoietic cells in intestinal inflammation.
  
  
  CONCLUSIONS
  The 5-HT7R 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.
authors: *Department of Cellular Neurophysiology, Institute for Neurophysiology, Hannover Medical School, Hannover, Germany; †Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany; ‡Institute of Immunology, Hannover Medical School, Hannover, Germany; and §Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors: Daria
authors: D
authors: Guseva
authors: Katrin
authors: K
authors: Holst
authors: Beate
authors: B
authors: Kaune
authors: Martin
authors: M
authors: Meier
authors: Lydia
authors: L
authors: Keubler
authors: Silke
authors: S
authors: Glage
authors: Manuela
authors: M
authors: Buettner
authors: André
authors: A
authors: Bleich
authors: Oliver
authors: O
authors: Pabst
authors: Oliver
authors: O
authors: Bachmann
authors: Evgeni G
authors: EG
authors: Ponimaskin
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology*; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D016753:Interleukin-10 / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011985:Receptors, Serotonin / Q000737:chemistry / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism; D055815:Young Adult
chemical_list: C556062:IL10 protein, mouse; D012333:RNA, Messenger; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D016753:Interleukin-10; D012701:Serotonin; D016264:Dextran Sulfate