Browsing by Subject "Intestinal inflammation"

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    P2X7 Receptor-Dependent Intestinal Afferent Hypersensitivity in a Mouse Model of Postinfectious Irritable Bowel Syndrome
    (Sociedad Americana de Inmunología, 2011) Keating, Christopher; Pelegrin, Pablo; Grundy, David; Martínez Cáceres, Carlos Manuel; Bioquímica y Biología Molecular B e Inmunología
    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.