THE PROTEIN-KINASE-C INHIBITOR, BISINDOLYLMALEIMIDE, INHIBITS THE TPA-INDUCED BUT NOT THE TNF-INDUCED INCREASE IN LLC-PK1 TRANSEPITHELIAL PERMEABILITY

The transepithelial paracellular permeability of an epithelium formed by LLC-PK1 cells increases upon activation of protein kinase C (PKC) b y the phorbol ester tumor promoter, TPA, or in response to the cytokin e tumor necrosis factor-alpha (TNF). Until recently, however, we have not been able to inhibit the permeability effects of TPA or TNF using any of the currently available serine-threonine kinase inhibitors. In this study we report that treatment of epithelial cell sheets with the selective PKC inhibitor bisindolylmaleimide, GF109203X, completely pr events the TPA-induced but not the TNF-alpha induced increase in tight junction permeability. While PKC-alpha still translocates from the cy tosol to the membrane of TPA-stimulated epithelial cells overall PKC a ctivity in the membrane fraction is markedly reduced in the presence o f GFX. (C) 1995 Academic Press, Inc.