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The Protein Kinase C Inhibitor, Bisindolylmaleimide, Inhibits the TPA-Induced But Not the TNF-Induced Increase in LLC-PK1 Transepithelial Permeability

1995; Elsevier BV; Volume: 209; Issue: 2 Linguagem: Inglês

10.1006/bbrc.1995.1551

1090-2104

Colleen Marano, K. V. Laughlin, Linda Russo, James M. Mullin,

Barrier Structure and Function Studies

The transepithelial paracellular permeability of an epithelium formed by LLC-PK1 cells increases upon activation of protein kinase C (PKC) by the phorbol ester tumor promoter, TPA, or in response to the cytokine tumor necrosis factor-α (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 prevents the TPA-induced but not the TNF-α induced increase in tight junction permeability. While PKC-α still translocates from the cytosol to the membrane of TPA-stimulated epithelial cells overall PKC activity in the membrane fraction is markedly reduced in the presence of GFX.