Inhibition of MAP kinase kinase (MEK) blocks endothelial PGI2 release but has no effect on von Willebrand factor secretion or E‐selectin expression
- 17 June 1996
- journal article
- Published by Wiley in FEBS Letters
- Vol. 388 (2-3) , 180-184
- https://doi.org/10.1016/0014-5793(96)00547-9
Abstract
We have examined the potential role of MAP kinase in the regulation of endothelial cell PGI2 synthesis, vWF secretion and E-selectin expression using the specific MEK inhibitor PD98059. PD98059 dose-dependently attenuated the tyrosine phosphorylation and activation of p42mapk in response to thrombin or inflammatory cytokines. Inhibition of thrombin-induced p42mapk activation was paralleled by an inhibitory effect of PD98059 on thrombin-driven PGI2 generation but not on vWF secretion or IL-1α/TNFα-induced E-selectin expression. These results provide evidence for a key role for p42mapk in the acute regulation of PGI2 synthesis in human endothelial cells and suggest that activation of the MAP kinase cascade is not obligatory for cytokine-stimulated E-selectin expression.Keywords
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