Intestinal inflammation

Enterochromaffin cell and 5-hydroxytryptamine responses to the same infectious agent differ in Th1 and Th2 dominant environments

Y Motomura^1,2, J-E Ghia¹, H Wang¹, H Akiho¹, R T El-Sharkawy¹, M Collins¹, Y Wan³, J T McLaughlin⁴, W I Khan¹

¹ Intestinal Diseases Research Program, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
² Department of Gastroenterology, Aso Iizuka Hospital, Iizuka, Japan
³ Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada
⁴ Department of Gastrointestinal Sciences, University of Manchester, Manchester, UK

Dr W I Khan, Room- 3N5D, McMaster University Medical Center, 1200 Main St West, Hamilton, Ontario L8N 3Z5, Canada; khanwal{at}mcmaster.ca

Background/aim: 5-Hydroxytryptamine (5-HT) released from enterochromaffin cells influences intestinal homeostasis by altering gut physiology and is implicated in the pathophysiology of various gut disorders. The mechanisms regulating 5-HT production in the gut remain unclear. This study investigated the T helper (Th) 1/Th2-based immunoregulation of enterochromaffin cell function and 5-HT production in a model of enteric infection.

Methods and results: Trichuris muris-infected AKR (susceptible to infection and generates Th1 response), BALB/c (resistant to infection and generates Th2 response), Stat4-deficient (impaired in Th1 response) and Stat6-deficient (impaired in Th2 response) mice were investigated to assess enterochromaffin cells, 5-HT and cytokines. In association with the generation of a Th2 response we observed higher enterochromaffin cell numbers and 5-HT content in the colon of BALB/c mice compared with AKR mice. Numbers of enterochromaffin cells and amount of 5-HT were significantly lower in Stat6-deficient mice after infection compared with Stat4-deficient mice. In addition, enterochromaffin cell numbers and 5-HT content were significantly higher after reconstitution of severe combined immunodeficient mice with in-vitro polarised Th2 cells.

Conclusion: The study demonstrated that enterochromaffin cell and 5-HT responses to the same infectious agent are influenced by Th1 or Th2 cytokine predominance and suggests that the immunological profile of the inflammatory response is important in the regulation of enterochromaffin cell biology in the gut. In addition to new data on enterochromaffin cell function in enteric infection and inflammation, this study provides important information on the immuno–endocrine axis in the gut, which may ultimately lead to improved strategies against gut disorders.

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