Persistent gut motor dysfunction in a murine model of T-cell-induced enteropathy.
BACKGROUND
Inflammatory bowel disease (IBD) patients in remission often experience irritable bowel syndrome (IBS)-like symptoms. We investigated the mechanism for intestinal muscle hypercontractility seen in T-cell-induced enteropathy in recovery phase.


METHODS
BALB/c mice were treated with an anti-CD3 antibody (100 microg per mouse) and euthanized at varying days post-treatment to investigate the histological changes, longitudinal smooth muscle cell contraction, cytokines (Th1, Th2 cytokines, TNF-alpha) and serotonin (5-HT)-expressing enterochromaffin cell numbers in the small intestine. The role of 5-HT in anti-CD3 antibody-induced intestinal muscle function in recovery phase was assessed by inhibiting 5-HT synthesis using 4-chloro-DL-phenylalanine (PCPA).


RESULTS
Small intestinal tissue damage was observed from 24 h after the anti-CD3 antibody injection, but had resolved by day 5. Carbachol-induced smooth muscle cell contractility was significantly increased from 4 h after injection, and this muscle hypercontractility was evident in recovery phase (at day 7). Th2 cytokines (IL-4, IL-13) were significantly increased from 4 h to day 7. 5-HT-expressing cells in the intestine were increased from day 1 to day 7. The 5-HT synthesis inhibitor PCPA decreased the anti-CD3 antibody-induced muscle hypercontractility in recovery phase.


CONCLUSIONS
Intestinal muscle hypercontractility in remission is maintained at the smooth muscle cell level. Th2 cytokines and 5-HT in the small intestine contribute to the maintenance of the altered muscle function in recovery phase.
Mizutani
T
T
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Akiho
H
H
Khan
W I
WI
Murao
H
H
Ogino
H
H
Kanayama
K
K
Nakamura
K
K
Takayanagi
R
R
D000704:Analysis of Variance; D000818:Animals; D017252:CD3 Complex / Q000276:immunology*; D002452:Cell Count; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004751:Enteritis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005769:Gastrointestinal Motility / Q000276:immunology*; D007150:Immunohistochemistry; D007422:Intestines / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000276:immunology*; D012701:Serotonin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D017252:CD3 Complex; D016207:Cytokines; D012701:Serotonin