Abstract
We have examined the potential role of MAP kinase in the regulation of endothelial cell PG12 synthesis, vWF secretion and E-selectin expression using the specific MEK inhibitor PD98059. PD98059 dose-dependently attenuated the tyrosine phosphorylation and activation of p42 mapk in response to thrombin or inflammatory cytokines. Inhibition of thrombin-induced p42 mapk activation was paralleled by an inhibitory effect of PD98059 on thrombin-driven PG12 generation but not on vWF secretion or IL-1 alpha/TNF alpha-induced E-selectin expression. These results provide evidence for a key role for p42 mapk in the acute regulation of PG12 synthesis in human endothelial cells and suggest that activation of the MAP kinase cascade is not obligatory for cytokine-stimulated E-selectin expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cells, Cultured
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E-Selectin / biosynthesis*
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E-Selectin / drug effects
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / enzymology*
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Epoprostenol / antagonists & inhibitors*
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Epoprostenol / metabolism
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Flavonoids / pharmacology
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Humans
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Interleukin-1 / metabolism
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Mitogen-Activated Protein Kinase 1
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Phosphorylation
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism*
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Thrombin / metabolism
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Tumor Necrosis Factor-alpha / metabolism
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Umbilical Veins
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von Willebrand Factor / drug effects
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von Willebrand Factor / metabolism*
Substances
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E-Selectin
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Enzyme Inhibitors
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Flavonoids
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Interleukin-1
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Tumor Necrosis Factor-alpha
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von Willebrand Factor
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Epoprostenol
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Protein-Tyrosine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Thrombin
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one