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

被引:42
作者
WheelerJones, CPD
May, MJ
Houliston, RA
Pearson, JD
机构
[1] Vascular Biology Research Centre, King's College London, Kensington, London W8 7AH, Campden Hill Road
关键词
human endothelial cell; MAP kinase; thrombin; cytokine; prostacyclin; adhesion molecule;
D O I
10.1016/0014-5793(96)00547-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:180 / 184
页数:5
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