title: Enhancement of intestinal inflammation in mice lacking interleukin 10 by deletion of the serotonin reuptake transporter.
abstract: BACKGROUND
  Enterochromaffin cells and enteric neurons synthesize and release serotonin (5-HT). Reuptake, mediated by a plasmalemmal transporter (SERT) terminates the action of released 5-HT. Serotonin secretion and serotonin reuptake transporter (SERT) expression have been reported to be decreased in TNBS-induced experimental colitis and in patients with ulcerative colitis. The present study was designed to utilize the transgenic deletion of SERT as a gain-of-function model to test the hypothesis that 5-HT is a pro-inflammatory mediator in experimental colitis.
  
  
  METHODS
  Colitis was compared in animals with IL10(+/+)SERT(+/+) (wild-type), IL10(-/-)SERT(+/+), IL10(-/-)SERT(+/-), and IL10(-/-)/SERT(-/-) (double knockout) genotypes. Macroscopic and histological damage scores were evaluated after a time period of up to 15 weeks.
  
  
  RESULTS
  Serotonin reuptake transporter expression was significantly increased in the inflamed colons of IL-10(-/-) mice, which displayed intestinal damage and a minor decrement in general health. General health was significantly worse and intestinal inflammation was more severe in IL-10(-/-)SERT(+/-), and IL-10(-/-)SERT(-/-) mice than in IL-10(-/-)SERT(+/+) or wild-type animals. Regardless of the associated SERT genotype, the number of 5-HT-immunoreactive cells was decreased by approximately 55-65% in all mice lacking IL-10.
  
  
  CONCLUSIONS
  Our observations indicate that colitis associated with IL-10 deficient mice is enhanced when the IL-10 deficiency is combined with a SERT deficiency. The data support the concept that 5-HT is a pro-inflammatory mediator in the gut.
authors.affiliation: Department of Nutritional Medicine and Immunology, University of Hohenheim, Stuttgart, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Haub
authors.forename: Y
authors.initials: Y
authors.lastname: Ritze
authors.forename: I
authors.initials: I
authors.lastname: Bergheim
authors.forename: O
authors.initials: O
authors.lastname: Pabst
authors.forename: M D
authors.initials: MD
authors.lastname: Gershon
authors.forename: S C
authors.initials: SC
authors.lastname: Bischoff
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics* / Q000502:physiology; D007410:Intestinal Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D016753:Interleukin-10