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Amplification loop of the inflammatory process is induced by P2X7R activation in intestinal epithelial cells in response to neutrophil transepithelial migration

Cesaro, Annabelle, Brest, Patrick, Hofman, Véronique, Hebuterne, Xavier, Wildman, Scott S.P., Ferrua, Bernard, Marchetti, Sandrine, Doglio, Alain, Vouret-Craviari, Valérie, Galland, Franck, and others. (2010) Amplification loop of the inflammatory process is induced by P2X7R activation in intestinal epithelial cells in response to neutrophil transepithelial migration. American Journal of Physiology: Gastrointestinal and Liver Physiology, 299 (1). G32-G42. ISSN 0193-1857. E-ISSN 1522-1547. (doi:10.1152/ajpgi.00282.2009) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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Abstract

Inflammatory bowel diseases (IBD) are characterized during their active phase by polymorphonuclear leukocyte (PMNL) transepithelial migration. The efflux of PMNL into the mucosa is associated with the production of proinflammatory cytokines and the release of ATP from damaged and necrotic cells. The expression and function of purinergic P2X7 receptor (P2X7R) in intestinal epithelial cells (IEC) and its potential role in the “cross talk” between IEC and PMNL have not been explored. The aims of the present study were 1) to examine P2X7R expression in IEC (T84 cells) and in human intestinal biopsies; 2) to detect any changes in P2X7R expression in T84 cells during PMNL transepithelial migration, and during the active and quiescent phases of IBD; and 3) to test whether P2X7R stimulation in T84 monolayers can induce caspase-1 activation and IL-1? release by IEC. We found that a functional ATP-sensitive P2X7R is constitutively expressed at the apical surface of IEC T84 cells. PMNL transmigration regulates dynamically P2X7R expression and alters its distribution from the apical to basolateral surface of IEC during the early phase of PMNL transepithelial migration in vitro. P2X7R expression was weak in intestinal biopsies obtained during the active phase of IBD. We show that activation of epithelial P2X7R is mandatory for PMNL-induced caspase-1 activation and IL-1? release by IEC. Overall, these changes in P2X7R function may serve to tailor the intensity of the inflammatory response and to prevent IL-1? overproduction and inflammatory disease.

Item Type: Article
DOI/Identification number: 10.1152/ajpgi.00282.2009
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Scott S.P. Wildman
Date Deposited: 10 Dec 2015 15:09 UTC
Last Modified: 29 May 2019 16:42 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/53060 (The current URI for this page, for reference purposes)
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