CHELERYTHRINE, A SELECTIVE PROTEIN-KINASE-C INHIBITOR, COUNTERACTS PYROGEN-INDUCED EXPRESSION OF TISSUE FACTOR WITHOUT EFFECT ON THROMBOMODULIN DOWN-REGULATION IN ENDOTHELIAL-CELLS

Endotoxin, interleukin1 beta(IL-1beta) and tumor necrosis factoralpha (TNF-alpha) dose-dependently increased the expression of tissue factor and at the same time induced thrombomodulin down-regulation on the su rface of cultured bovine aortic endothelial cells. Chelerythrine, a se lective protein kinase C inhibitor, strongly reduced endotoxin-, IL1 b eta- and TNFalpha-induced tissue factor expression but remained withou t effect with regard to thrombomodulin down-regulation measured in par allel. On the contrary, staurosporine, a highly potent, non-selective PKC inhibitor, simultaneously abolished tissue factor expression and t hrombomodulin down-regulation induced by endotoxin, IL1beta and TNFalp ha. These results show that protein kinase C is deeply involved in the process leading to pyrogen-induced tissue factor expression and sugge st that thrombomodulin down-regulation is regulated by a different pat hway.