Protein kinase C regulates cytokine-induced tissue factor transcription and procoagulant activity in human endothelial cells
Abstract
Interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) induce tissue factor in endothelium, which results in activation of the coagulation cascade. Despite extensive investigation, in which various stimuli that induce tissue factor have been defined, the intracellular processes that control tissue factor expression are not well understood. It has been proposed that protein kinase C regulates tissue factor expression primarily because phorbol myristate acetate, the protein kinase C activator, induces tissue factor expression. In this study we examined whether IL-1 alpha- or TNF-alpha-stimulated tissue factor production is regulated through a protein kinase C-dependent mechanism. Northern blot analysis showed that cytokine-induced tissue factor mRNA was significantly reduced in human umbilical vein endothelial cells treated with calphostin C, a specific protein kinase C inhibitor. Tissue factor functional activity was decreased in the presence of calphostin C as well. Calphostin C also inhibited phorbol myristate acetate-induced tissue factor expression. In contrast, calphostin C did not alter cytokine induction of E-selectin or prostacyclin release. Because calcium stimulates protein kinase C binding to the...Continue Reading
References
Translocation of spectrin and protein kinase C to a cytoplasmic aggregate upon lymphocyte activation
Tumor necrosis factor-alpha, a new tumor promoter, engendered by biochemical studies of okadaic acid
12-Deoxyphorbol-13-O-phenylacetate-20-acetate is not protein kinase C-beta isozyme-selective in vivo
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