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) by the phorbol ester tumor promoter, TPA, or in response to the cytokine 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 the treatment of epithelial cell sheets with the selective PKC inhibitor bisindolylmaleimide, GF109203X, completely prevents the TPA-induced but not the TNF-alpha induced increase in tight junction permeability. While PKC-alpha 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.
Marano
C W
CW
Lankenau Medical Research Center, Wynnewood, PA 19096, USA.
Laughlin
K V
KV
Russo
L M
LM
Mullin
J M
JM
D000818:Animals; D004848:Epithelium / Q000187:drug effects*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D018374:LLC-PK1 Cells; D008301:Maleimides / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D007211:Indoles; D008301:Maleimides; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate