Enhancement of intestinal inflammation in mice lacking interleukin 10 by deletion of the serotonin reuptake transporter
Open Access
- 8 March 2010
- journal article
- research article
- Published by Wiley in Neurogastroenterology & Motility
- Vol. 22 (7), 826-e229
- https://doi.org/10.1111/j.1365-2982.2010.01479.x
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. 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 ∼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.Keywords
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