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Colonic luminal proteases activate colonocyte proteinase‐activated receptor‐2 and regulate paracellular permeability in mice
Author(s) -
Róka R.,
Demaude J.,
Cenac N.,
Ferrier L.,
Salvadorcartier C.,
Garciavillar R.,
Fioramonti J.,
Bueno L.
Publication year - 2007
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2006.00851.x
Subject(s) - proteases , protease , trypsin , protease activated receptor 2 , paracellular transport , chemistry , receptor , mast cell , pharmacology , intestinal permeability , serine protease , biochemistry , biology , enzyme , permeability (electromagnetism) , immunology , enzyme linked receptor , membrane
Luminal activation of protease‐activated receptors‐2 (PAR 2 ) on colonocytes by trypsin or PAR 2 ‐activating peptide increases colonic paracellular permeability (CPP). The aim of this study was to evaluate the role of proteases from endogenous and bacterial origin in the modulation of CPP and colonocyte PAR 2 expression in mice. CPP was assessed with 51 Cr‐EDTA after intracolonic administration of different protease inhibitors. After 12 days of oral antibiotic treatment, measurements of colonic luminal serine protease activity (CLSPA), CPP, mucosal mouse mast cell proteinase‐1 (MMCP‐1) content, immunochemistry of PAR 2 and assessment of effects of PAR 2 agonist (SLIGRL) and mast cell degranulator (C48/80) on CPP in Ussing chambers were performed. Immunochemistry was repeated after intracolonic trypsin administration. Colonic infusion of protease inhibitors significantly reduced CPP. In antibiotic‐treated mice, CLSPA was reduced coupled with a decrease in PAR 2 expression, but with no change in CPP and MMCP‐1 content. Trypsin administration restored PAR 2 expression. The increase in CPP induced by SLIGRL and C48/80 was reduced after antibiotic treatment. Protease activity of colonic content plays an important role in the regulation of mucosal barrier through activation of PAR 2 .