Inhibition of MAP kinase kinase (MEK) blocks endothelial PGI2 release but has no effect on von Willebrand factor secretion or E‐selectin expression

[摘要]

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 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 PGI₂ generation but not on vWF secretion or IL-1α/TNFα-induced E-selectin expression. These results provide evidence for a key role for p42^mapk 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.

[学科分类] 生物化学/生物物理

[关键词] Human endothelial cell;MAP kinase;Thrombin;Cytokine;Prostacyclin;Adhesion molecule;HUVEC;human umbilical vein endothelial cell;MAP kinase;mitogen activated protein kinase;MEK;MAP kinase kinase;p42mapk;42 kDa MAP kinase;p44mapk;44 kDa MAP kinase;PGI2;prostacyclin;vWF;von Willebrand Factor;GPCA;G protein-coupled agonist