P2X7 Receptor-Dependent Intestinal Afferent Hypersensitivity in a Mouse Model of Postinfectious Irritable Bowel Syndrome
2011
The ATP-gated P2X 7 receptor (P2X 7 R) was shown to be an important mediator of inflammation and inflammatory pain through its regulation of IL-1β processing and release. Trichinella spiralis -infected mice develop a postinflammatory visceral hypersensitivity that is reminiscent of the clinical features associated with postinfectious irritable bowel syndrome. In this study, we used P2X 7 R knockout mice (P2X 7 R −/− ) to investigate the role of P2X 7 R activation in the in vivo production of IL-1β and the development of postinflammatory visceral hypersensitivity in the T. spiralis -infected mouse. During acute nematode infection, IL-1β–containing cells and P2X 7 R expression were increased in the jejunum of wild-type (WT) mice. Peritoneal and serum IL-1β levels were also increased, which was indicative of elevated IL-1β release. However, in the P2X 7 R −/− animals, we found that infection had no effect upon intracellular, plasma, or peritoneal IL-1β levels. Conversely, infection augmented peritoneal TNF-α levels in both WT and P2X 7 R −/− animals. Infection was also associated with a P2X 7 R-dependent increase in extracellular peritoneal lactate dehydrogenase, and it triggered immunological changes in both strains. Jejunal afferent fiber mechanosensitivity was assessed in uninfected and postinfected WT and P2X 7 R −/− animals. Postinfected WT animals developed an augmented afferent fiber response to mechanical stimuli; however, this did not develop in postinfected P2X 7 R −/− animals. Therefore, our results demonstrated that P2X 7 Rs play a pivotal role in intestinal inflammation and are a trigger for the development of visceral hypersensitivity.
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