P2X 7 receptor-dependent intestinal afferent hypersensitivity in a mouse model of postinfectious irritable bowel syndrome

摘要

The ATP-gated P2X7 receptor (P2X7R) was shown to be an important mediator of inflammation and inflammatory pain through its regulation of IL-1?? 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 P2X7R knockout mice (P2X7R-/-) to investigate the role of P2X7R activation in the in vivo production of IL-1?? and the development of postinflammatory visceral hypersensitivity in the T. spiralis-infected mouse. During acute nematode infection, IL-1??-containing cells and P2X7R expression were increased in the jejunum of wild-type (WT) mice. Peritoneal and serum IL-1?? levels were also increased, which was indicative of elevated IL-1?? release. However, in the P2X7R-/- animals, we found that infection had no effect upon intracellular, plasma, or peritoneal IL-1?? levels. Conversely, infection augmented peritoneal TNF-?? levels in both WT and P2X7R-/- animals. Infection was also associated with a P2X7R-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 P2X7R-/- animals. Postinfected WT animals developed an augmented afferent fiber response to mechanical stimuli; however, this did not develop in postinfected P2X7R-/- animals. Therefore, our results demonstrated that P2X7Rs play a pivotal role in intestinal inflammation and are a trigger for the development of visceral hypersensitivity. Copyright ?? 2011 by The American Association of Immunologists, Inc.