Effect of eicosapentaenoic acid (EPA) on tight junction permeability in intestinal monolayer cells

The purpose of this study is to evaluate the effect of C18 and C20 long cha in fatty acids on tight junction permeability in a model of intestinal epit helium. Methods: Confluent Caco-2 cells on porous filters with double chamb er system were used to measure fluorescein sulfonic acid (FS) permeability and transepithelial electrical resistance (TEER). Lactate dehydrogenase rel ease and ultrastructure were evaluated. Effect of 200 muM eicosapentaenoic acid (EPA, C20:5 n-3), arachidonic acid (AA, C20:4 n-6), alpha -linoleic ac id (ALA, C18:3 n-3), linoleic acid (LA, C18:2 n-6), or oleic acid (OA, C18: 1 n-9) enrichment in the culture medium during 24 hours were compared. The effect of the cyclooxygenase inhibitor, indomethacin, lipoxygenase inhibit ors, NDGA or AA861, and antioxidant, BHT, was evaluated as a mechanism to c hange tight junction permeability. Results: Caco-2 cells formed polarized c olumner epithelial cells with densely packed microvilli and well developed junctional complexes. Addition of EPA enhanced FS permeability to 3.0 +/- 1 .6-fold and lowered TEER to 0.59 +/- 1.2-fold vs. control with concentratio n dependency without cell injury (P< 0.01-0.05). OA, AA or LA did not chang e, but ALA enhanced tight junction permeability. Indomethacin and AA861 nor malized the changes mediated by EPA. Conclusions., EPA affects tight juncti on permeability in intestinal monolayer cells specifically and concentratio n dependently via cyclooxygenase and lipoxygenase products. (C) 2001 Harcou rt Publishers Ltd.