Publication: P2X7 Receptor-Dependent Intestinal Afferent Hypersensitivity in a Mouse Model of Postinfectious Irritable Bowel Syndrome
Authors
Keating, Christopher ; Pelegrin, Pablo ; Grundy, David ; Martínez Cáceres, Carlos Manuel
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Publisher
Sociedad Americana de Inmunología
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DOI
https://doi.org/10.4049/jimmunol.1100423
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info:eu-repo/semantics/article
Description
©2011. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This document is the Accepted, version of a Published Work that appeared in final form in Journal of Immunology. To access the final edited and published work see https://doi.org/10.4049/jimmunol.1100423
Abstract
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.
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Citation
Journal of Immunology, volumen 87, nº 3, año 2011, páginas 1467-1474
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/