Journal
NEUROGASTROENTEROLOGY AND MOTILITY
Volume 22, Issue 7, Pages -Publisher
WILEY
DOI: 10.1111/j.1365-2982.2010.01479.x
Keywords
colitis; inflammation; interleukin 10; serotonin; serotonin reuptake transporter
Funding
- Columbia University
- Land Baden-Wurttemberg
- Zentrum fur Ernahrungsmedizin of the Universities of Hohenheim and Tubingen, Germany
Ask authors/readers for more resources
P>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. Key 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 similar to 55-65% in all mice lacking IL-10. Conclusions & Inferences 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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available