title: Changes in Epithelial Barrier Function in Response to Parasitic Infection: Implications for IBD Pathogenesis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Joan Antoni
authors.initials: JA
authors.lastname: Fernández-Blanco
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Estévez
authors.affiliation: University of Maryland School of Medicine, Division of Gastroenterology & Hepatology and Mucosal Biology Research Center, Baltimore, MD, USA.
authors.forename: Terez
authors.initials: T
authors.lastname: Shea-Donohue
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain Instituto de Neurociencias, Universitat Autònoma de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain vicente.martinez@uab.es.
authors.forename: Vicente
authors.initials: V
authors.lastname: Martínez
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain Instituto de Neurociencias, Universitat Autònoma de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Patri
authors.initials: P
authors.lastname: Vergara
mesh_terms: D000818:Animals; D053818:Chymases / Q000378:metabolism; D062446:Claudin-2 / Q000378:metabolism; D062465:Claudin-3 / Q000378:metabolism; D006965:Hyperplasia / Q000469:parasitology; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000469:parasitology / Q000473:pathology* / Q000503:physiopathology*; D007583:Jejunum / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000201:enzymology*; D062793:Occludin / Q000378:metabolism; D010539:Permeability; D052336:Proglucagon / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000378:metabolism*; D046509:Tissue Culture Techniques; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000503:physiopathology*; D053802:Tryptases / Q000378:metabolism
chemical_list: D062446:Claudin-2; D062465:Claudin-3; D015850:Interleukin-6; D062793:Occludin; D052336:Proglucagon; D053818:Chymases; D053802:Tryptases
keywords: Epithelial permeability; Trichinella spiralis; mast cell proteinases; post-infectious; tight junction
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