Protease-activated receptor 2 and gut permeability: a review

Authors


Lionel Bueno, Neurogastroenterology and Nutrition Unit, INRA, 180 Chemin de Tournefeuille, BP 3, F-31931 Toulouse Cedex 9, France.
Tel: +33 561 28 51 43; fax: +33 561 28 53 97; e-mail: lbueno@toulouse.inra.fr

Abstract

Abstract  Digestive tract proteases are best known for their proteolytic activity in the digestion of alimentary proteins. However, during the last decade, a possible role of proteases as signalling molecules has been emphasized with the discovery of a novel class of G-protein coupled receptors located on cell membranes that may be activated by proteolytic cleavage of their N-terminal extracellular domain. Type 2 protease-activated receptors (PAR-2) are cleaved by serine-proteases such as trypsin and tryptase. PAR-2 is present in many intestinal cell types and particularly on epithelial cells. Multiple functions have been demonstrated in the gut for PAR-2, including epithelial permeability, mainly the intercellular permeability that is of paramount importance in the equilibrium between the external milieu (digestive contents) and the submucosal immune system. Alterations of both tissue and luminal levels of proteases or serine-protease activity may affect gut permeability and subsequently the immune status of the mucosa. Activation of PAR-2 on epithelial cells may directly affect cytoskeleton contraction by triggering phosphorylation of myosin light chain with subsequent changes in tight junction permeability. Enhanced fecal protease level has been recently reported in both organic (ulcerative colitis) and functional (irritable bowel syndrome) intestinal disorders and may play a role in the pathogenesis of such diseases.

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