Persistent gut motor dysfunction in a murine model of T-cell-induced enteropathy

T. Mizutani, H. Akiho, W. I. Khan, H. Murao, H. Ogino, K. Kanayama, K. Nakamura, R. Takayanagi

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14 Citations (Scopus)

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 μg per mouse) and euthanized at varying days post-treatment to investigate the histological changes, longitudinal smooth muscle cell contraction, cytokines (Th1, Th2 cytokines, TNF-α) 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). Key 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 & Inferences 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.

Original languageEnglish
Pages (from-to)196-203+e65
JournalNeurogastroenterology and Motility
Volume22
Issue number2
DOIs
Publication statusPublished - Feb 1 2010

All Science Journal Classification (ASJC) codes

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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    Mizutani, T., Akiho, H., Khan, W. I., Murao, H., Ogino, H., Kanayama, K., Nakamura, K., & Takayanagi, R. (2010). Persistent gut motor dysfunction in a murine model of T-cell-induced enteropathy. Neurogastroenterology and Motility, 22(2), 196-203+e65. https://doi.org/10.1111/j.1365-2982.2009.01396.x