Expression und Verteilung der Tight Junction Proteine Occludin und ZO-1 in der akuten und chronischen Dextransulfat-induzierten Colitis der Maus

Abstract

Introduction: The intestinal epithelium serves as dynamic barrier and allows a regulated resorption of molecules and water. Changes in expression or a redistribution of intercellular tight junction (TJ) proteins regulating paracellular permeability could increase intestinal permeability and play a role in the pathogenesis of inflammatory bowel disease (IBD). We examined epithelial permeability, and expression and distribution of TJ proteins occludin and zonula occludens (ZO)-1 in acute and chronic DSS-Colitis, an experimental model of IBD. Methods: The colonic tissue of three different groups was examined (n = 10 animals each): healthy control, acute DSS colitis (5% w/v DSS in drinking water for 7 days) and chronic colitis (cyclic application of DSS 3% w/v for 30 days). The tissue was incubated with Lanthanum, and permeability for Lanthanum was quantified by electron microscopy. Cryosections were used for Western blots and for immunofluorescence for occludin and ZO-1. Colitis activity was evaluated by a clinical and histological disease activity index. Scores were compared by the Kruskal-Wallis-Test (P < 0.05). Results: DSS led to a pronounced acute or chronic colitis with clinical and histological disease activity. Epithelial permeability for Lanthanum was increased compared to controls in both groups. In acute colitis, expression of occludin and ZO-1 was reduced at the apical membrane as measured by Western blot and immunofluorescence. Occludin was internalized into epithelial cells. In chronic colitis, only marginal changes in TJ protein expression were noted. Discussion: Redistribution and decreased expression of TJ proteins might explain the increased epithelial permeability in IBD. In acute inflammation the changes are more pronounced than in chronic inflammation. Internalization of TJ proteins might be a step in the disassembly of TJ, but a recycling mechanism with rapid reassembly seems possible.