Affiliations: Laboratory of Cardiovascular Diseases, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, P. R. China | Institute of Biomedical Engineering, West China Center of Medical Sciences, Sichuan University, Chengdu 610041, Sichuan, P. R. China | School of Electrical Engineering and Information, Sichuan University, Chengdu 610041, Sichuan, P. R. China
Note: [] Address for correspondence: Prof. Huaiqing Chen, Institute of Biomedical Engineering, West China Center of Medical Sciences, Sichuan University, Chengdu 610041, Sichuan, China. Tel.: +86 28 5503400; Fax: +86 28 85503400; E-mail: [email protected].
Abstract: Shear stress can modulate endothelial cell function by regulating gene expression. We have previously demonstrated that low shear stress (4.2 dyn/cm2) induces the expression of interleukin-8 (IL-8) gene in endothelial cells. The present study was undertaken to further investigate both the effects of shear stress on IL-8 expression and the mechanisms controlling IL-8 mRNA up-regulation in human umbilical vein endothelial cells (HUVEC). We show that shear stress (from 2.23 to 19.29 dyn/cm2) induces the IL-8 expression at both the mRNA and protein levels by stimulating transcription. In order to determine the possible contribution of G protein, HUVEC were pretreated with an inhibitor of G-protein activation, GDPβS, which abrogated the low shear stress-induced IL-8 gene expression. Such gene expression was also partially inhibited by the tyrosine kinase inhibitor (tyrphostin-25) and in addition by EGTA, BATPA/AM (the intracellular Ca2+ chelator), Verapamil (a Ca2+ channel blocker), cAMP-dependent protein kinase inhibitor (KT5720) and phospholipase C inhibitor (neomycin). However, the cGMP-dependent protein kinase inhibitor, KT5823, had no effect on such expression. These findings therefore demonstrate the involvement of several signaling molecules, including tyrosine kinase, G protein, calcium, phospholipase C, and cAMP-dependent protein kinase, in the low shear stress-induced IL-8 gene expression.
Keywords: Endothelial cells, interleukin-8, signal transduction
Journal: Biorheology, vol. 44, no. 5-6, pp. 349-360, 2007
