Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice
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Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice. / Bischoff, Stephan C; Mailer, Reiner; Pabst, Oliver; Weier, Gisela; Sedlik, Wanda; Li, Zhishan; Chen, Jason J; Murphy, Dennis L; Gershon, Michael D.
In: AM J PHYSIOL-GASTR L, Vol. 296, No. 3, 03.2009, p. G685-95.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Role of serotonin in intestinal inflammation: knockout of serotonin reuptake transporter exacerbates 2,4,6-trinitrobenzene sulfonic acid colitis in mice
AU - Bischoff, Stephan C
AU - Mailer, Reiner
AU - Pabst, Oliver
AU - Weier, Gisela
AU - Sedlik, Wanda
AU - Li, Zhishan
AU - Chen, Jason J
AU - Murphy, Dennis L
AU - Gershon, Michael D
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
KW - Animals
KW - Colitis/chemically induced
KW - Colon/physiology
KW - Gastrointestinal Motility/immunology
KW - Histamine/metabolism
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Peroxidase/metabolism
KW - Rectum/physiology
KW - Serotonin/metabolism
KW - Serotonin Plasma Membrane Transport Proteins/genetics
KW - Trinitrobenzenesulfonic Acid/toxicity
U2 - 10.1152/ajpgi.90685.2008
DO - 10.1152/ajpgi.90685.2008
M3 - SCORING: Journal article
C2 - 19095763
VL - 296
SP - G685-95
JO - AM J PHYSIOL-GASTR L
JF - AM J PHYSIOL-GASTR L
SN - 0193-1857
IS - 3
ER -
