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Am J Physiol Gastrointest Liver Physiol (July 24, 2003). doi:10.1152/ajpgi.00073.2003
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Submitted on February 14, 2003
Accepted on July 22, 2003

INTERLEUKIN-1{beta} ACTIVATES SPECIFIC POPULATIONS OF ENTERIC NEURONS AND ENTERIC GLIA IN THE GUINEA PIG ILEUM AND COLON

Eric T. T. L. Tjwa1, Joelle M. Bradley2, Catherine M. Keenan2, Alfons B. A. Kroese3, and Keith A. Sharkey2*

1 Gastrointestinal and Neuroscience Research Groups, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada; Departments of Medical Physiology and Surgery, University Medical Centre, Utrecht, The Netherlands; Department of Gastroenterology, University of Medical Centre, Nijmegen, The Netherlands
2 Gastrointestinal and Neuroscience Research Groups, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada
3 Departments of Medical Physiology and Surgery, University Medical Centre, Utrecht, The Netherlands

* To whom correspondence should be addressed. E-mail: ksharkey{at}ucalgary.ca.

Fos expression was used to assess whether the proinflammatory cytokine interleukin-1{beta} (IL-1{beta}) activated specific, chemically-coded neuronal populations in isolated preparations of guinea pig ileum and colon. Whether the effects of IL-1{beta} were mediated through a prostaglandin pathway and if IL-1{beta} induced the expression of cyclooxygenase (COX)-2 was also examined. Single and double-labelling immunohistochemistry was used after treatment of isolated tissues with IL-1{beta} (0.1-10ng/ml). IL-1{beta} induced Fos expression in enteric neurons and also in enteric glia in the ileum and colon. For enteric neurons, activation was concentration-dependent and sensitive to indomethacin, in both the myenteric and submucosal plexuses, in both regions of the gut. The maximum proportion of activated neurons differed between the ileal (~15%) and colonic (~42%) myenteric and ileal (~60%) and colonic (~75%) submucosal plexuses. The majority of neurons that were activated in the myenteric plexus of the ileum expressed nitric oxide synthase (NOS) or enkephalin immunoreactivity. In the colon, activated myenteric neurons expressed NOS. In the submucosal plexus of both regions of the gut the majority of activated neurons were vasoactive intestinal polypeptide (VIP) immunoreactive. After treatment with IL-1{beta}, COX-2 immunoreactivity was detected in the wall of the gut in both neurons and non-neuronal cells. In conclusion, we have found that the proinflammatory cytokine IL-1{beta} specifically activates certain neurochemically defined neural pathways and that these changes may lead to disturbances in motility observed in the inflamed bowel.




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