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

Research output: Contribution to journalArticle

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

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Serotonin
T-Lymphocytes
Muscles
Anti-Idiotypic Antibodies
Cytokines
Smooth Muscle Myocytes
Recovery of Function
Small Intestine
Enterochromaffin Cells
Fenclonine
Injections
Interleukin-13
Irritable Bowel Syndrome
Carbachol
Muscle Contraction
Inflammatory Bowel Diseases
Interleukin-4
Intestines
Cell Count
Maintenance

All Science Journal Classification (ASJC) codes

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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Persistent gut motor dysfunction in a murine model of T-cell-induced enteropathy. / Mizutani, T.; Akiho, H.; Khan, W. I.; Murao, H.; Ogino, H.; Kanayama, K.; Nakamura, K.; Takayanagi, R.

In: Neurogastroenterology and Motility, Vol. 22, No. 2, 01.02.2010, p. 196-203+e65.

Research output: Contribution to journalArticle

Mizutani, T, Akiho, H, Khan, WI, 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, vol. 22, no. 2, pp. 196-203+e65. https://doi.org/10.1111/j.1365-2982.2009.01396.x
Mizutani, T. ; Akiho, H. ; Khan, W. I. ; Murao, H. ; Ogino, H. ; Kanayama, K. ; Nakamura, K. ; Takayanagi, R. / Persistent gut motor dysfunction in a murine model of T-cell-induced enteropathy. In: Neurogastroenterology and Motility. 2010 ; Vol. 22, No. 2. pp. 196-203+e65.
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N2 - 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.

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