title: Persistent gut motor dysfunction in a murine model of T-cell-induced enteropathy.
abstract: 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.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mizutani
authors.forename: H
authors.initials: H
authors.lastname: Akiho
authors.forename: W I
authors.initials: WI
authors.lastname: Khan
authors.forename: H
authors.initials: H
authors.lastname: Murao
authors.forename: H
authors.initials: H
authors.lastname: Ogino
authors.forename: K
authors.initials: K
authors.lastname: Kanayama
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: R
authors.initials: R
authors.lastname: Takayanagi
mesh_terms: 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
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D012701:Serotonin