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OBJECTIVES:

The objective of this study was to investigate how mast cell tryptase may influence intestinal permeability and tight junction (TJ) proteinsin vitroand explore translation to irritable bowel syndrome (IBS).

METHODS:

We investigated the effect of:(1) tryptase on Caco-2 monolayers,(2) mast cell degranulation in a Caco-2/human mast cell-1 (HMC-1) co-culture model,(3) mast cell degranulation±tryptase inhibition with nafamostat mesilate (NM). Epithelial integrity was assessed by transepithelial resistance (TER), permeability to fluorescein isothiocyanate (FITC)-dextran and transmission electron microscopy (TEM). The expression of junctional proteins zonula occludens-1 (ZO-1), junctional adhesion molecule-A (JAM-A), claudin-1 (CLD-1), CLD-2, CLD-3, occludin and E-cadherin was determined by western blot analysis and immunofluorescence confocal microscopy. Based on thein vitroresults, we further …