[Inhibition of CD40L induced E-selectin expression in endothelial cells through extracellular signal-regulated kinase signaling pathway].
OBJECTIVE
To investigate the regulatory effects of atorvastatin on CD40L induced E-selectin expression in endothelial cells and the association thereof with signal pathway.


METHODS
Human umbilical vein endothelial cells (HUVECs) were obtained from umbilical cord newly delivered and incubated with CD40L for 24 hours with or without pretreated by atorvastatin of the concentrations of 0.1, 1, or 10 micromol/L. The protein and mRNA levels of E-selectin were detected by flow cytometry and reverse transcription polymerase chain reaction (RT-PCR) respectively. The extracellular signal regulated kinase (ERK) 1/2 activation was analyzed by Western blotting.


RESULTS
The E-selectin mRNA expression level of the HUVECs treated by atorvastatin was lower than that of the CD40L stimulation group by 33.33% when the atorvastatin concentration was 1 micromol/L, and was lower by 45.16% when the atorvastatin concentration was 10 micromol/L. The E-selectin protein expression level of the HUVECs treated by atorvastatin was lower than that of the CD40L stimulation group by 48.68% when the atorvastatin concentration was 1 micromol/L, and was lower by 70.25% when the atorvastatin concentration was 10 micromol/L. The phosphorylation level of ERK1/2 was enhanced by CD40L stimulation and the CD40L induced phosphorylation of ERK1/2 decreased by 81% +/- 6%, 73% +/- 5%, and 41% +/- 5% respectively after atorvastatin stimulation.


CONCLUSIONS
Atorvastatin decreases the CD40L induced E-selectin expression in endothelial cells while atorvastatin at 0.1-10 micromol/L concentration-dependently through inhibiting the activation of ERK1/2.
Xia
Zun-en
ZE
Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Li
Yan
Y
Wang
Ming
M
Wu
Qing
Q
D000069059:Atorvastatin; D023201:CD40 Ligand / Q000378:metabolism; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D019040:E-Selectin; D006538:Heptanoic Acids; D011758:Pyrroles; D023201:CD40 Ligand; D000069059:Atorvastatin; D020928:Mitogen-Activated Protein Kinases