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Enterochromaffin cell and 5-hydroxytryptamine responses to the same infectious agent differ in Th1 and Th2 dominant environments
  1. Yasuaki Motomura
  1. Intestinal Disease Research Program, McMaster University, Canada
    1. Jean-Eric Ghia
    1. Intestinal Disease Research Program, McMaster University, Canada
      1. Huaqing Wang
      1. Intestinal Disease Research Program, McMaster University, Canada
        1. Hirotada Akiho
        1. Intestinal Disease Research Program, McMaster University, Canada
          1. Rami T El-Sharkawy
          1. Intestinal Disease Research Program, McMaster University, Canada
            1. Matthew Collins
            1. Intestinal Disease Research Program, McMaster University, Canada
              1. Yonghong Wan
              1. Intestinal Disease Research Program, McMaster University, Canada
                1. John T McLaughlin
                1. University of Manchester, United Kingdom
                  1. Waliul I Khan (khanwal{at}mcmaster.ca)
                  1. Intestinal Disease Research Program, McMaster University, Canada

                    Abstract

                    Background/Aim: 5-hydroxytryptamine (5-HT) released from enterochromaffin (EC) cells influences intestinal homeostasis by altering gut physiology and is implicated in the pathophysiology of various gut disorders. However, the mechanisms regulating 5-HT production in the gut remain unclear. This study investigated the Th1/Th2 based immuno-regulation of EC cell function and 5-HT production in a model of enteric infection.

                    Methods & 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 EC cells, 5-HT and cytokines. In association with generation of Th2 response we observed higher EC cells numbers and 5-HT amount in colon of BALB/c mice compared to AKR mice. Numbers of EC cells and amount of 5-HT were significantly lower in Stat6 deficient mice following infection as compared to Stat4 deficient mice. In addition, EC cells numbers and 5-HT amount were significantly higher following reconstitution of SCID mice with in vitro polarized Th2 cells.

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

                    • 5-HT
                    • Enteric Infection
                    • Enterochromaffin cell
                    • Stat4/Stat6
                    • Th1/Th2

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