Submitted on December 4, 2008
Accepted on December 10, 2008
Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice
Stephan C. Bischoff1*, Rainer Mailer2, Oliver Pabst2, Gisela Weier2, Wanda Sedlik3, Zhishan Li3, Jason J. Chen3, Dennis L. Murphy4, and Michael D Gershon3
1 University of Hohenheim
2 Medical School of Hannover
3 Columbia University
4 National Institute of Mental Health
* To whom correspondence should be addressed. E-mail: bischoff.stephan{at}uni-hohenheim.de.
Objective: Serotonin (5-HT) regulates peristaltic and secretory reflexes in the gut. The serotonin reuptake transporter (SERT; SLC6A4), which inactivates 5-HT, is expressed in the intestinal mucosa and the enteric nervous system (ENS). Stool water content is increased and colonic motility is irregular in mice with a targeted deletion of SERT. We tested the hypotheses that 5-HT plays a role in regulating intestinal inflammation and that the potentiation of serotonergic signaling that results from SERT deletion is proinflammatory. Methods: Rectal installation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce an immune-mediated colitis, which was compared in SERT knockout mice and littermate controls. Results: Intestinal myeloperoxidase (MPO) and histamine levels were significantly increased, while the survival rate and state of health were significantly decreased in TNBS-treated mice that lacked SERT. Deletion of SERT thus increases the severity of TNBS colitis. Conclusions: These data suggest that 5-HT and its SERT-mediated termination play roles in intestinal immune/inflammatory responses in mice.
