Changes in epithelial barrier function in response to parasitic infection: Implications for IBD pathogenesis

Joan Antoni Fernández-Blanco, Javier Estévez, Terez Shea-Donohue, Vicente Martínez, Patri Vergara

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

© 2015 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. Background and aims: Mast cells [MCs] are implicated in epithelial barrier alterations that characterize inflammatory and functional bowel disorders. In this study, we describe mast cell proteinases [chymases and tryptases] and tight junction [TJ] proteins kinetics in a rat model of postinfectious gut dysfunction. Methods: Jejunal tissues of control and -infected rats were used. Inflammation-related changes in MCs and the expression of TJ-related proteins were evaluated by immunostaining and reverse transcription-quantitative polymerase chain reaction. Epithelial barrier function was assessed in vitro (Ussing chambers) and in vivo. Results: After infection, intestinal inflammation was associated with a generalized overexpression of MC chymases, peaking between Days 6 and 14. Thereafter, a mucosal MC hyperplasia and a late increase in connective tissue MC counts were observed. From Day 2 post-infection, TJ proteins occludin and claudin-3 expression was down-regulated whereas the pore-forming protein claudin-2 was overexpressed. The expression of proglucagon, precursor of the barrier-enhancing factor glucagon-like peptide-2, was reduced. These changes were associated with an increase in epithelial permeability, both in vitro and in vivo. Conclusions: Proteinases expression and location of mucosal and connective tissue MCs indicate a time-related pattern in the maturation of intestinal MCs following infection. Altered expression of TJ-related proteins is consistent with a loss of epithelial tightness, and provides a molecular mechanism for the enhanced epithelial permeability observed in inflammatory conditions of the gut. Copyright
Original languageEnglish
Pages (from-to)463-476
JournalJournal of Crohn's and Colitis
Volume9
Issue number6
DOIs
Publication statusPublished - 1 Jun 2015

Keywords

  • Epithelial permeability
  • mast cell proteinases
  • post-infectious
  • tight junction
  • Trichinella spiralis

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