Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice.
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. 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. 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. Intestinal myeloperoxidase and histamine levels were significantly increased, whereas 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. These data suggest that 5-HT and its SERT-mediated termination play roles in intestinal immune/inflammatory responses in mice.
Bischoff
Stephan C
SC
Department of Nutritional Medicine and Immunology, University of Hohenheim, D-70593 Stuttgart, Germany. bischoff.stephan@uni-hohenheim.de
Mailer
Reiner
R
Pabst
Oliver
O
Weier
Gisela
G
Sedlik
Wanda
W
Li
Zhishan
Z
Chen
Jason J
JJ
Murphy
Dennis L
DL
Gershon
Michael D
MD
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000401:mortality / Q000503:physiopathology*; D003106:Colon / Q000502:physiology; D005769:Gastrointestinal Motility / Q000276:immunology; D006632:Histamine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D012007:Rectum / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D012701:Serotonin; D006632:Histamine; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase