Inhibition of MAP kinase kinase (MEK) blocks endothelial PGI(2) release but has no effect on von Willebrand Factor secretion or E-selectin expression

We have examined the potential role of MAP kinase in the regulation of endothelial cell PGI(2) 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 PGI(2) 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 PGI(2) synthesis in human endothelial cells and suggest that activation of the MAP kinase cascade is not obligatory for cytokine-stimulated E-selectin expression.