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  • Title: IL-8 gene induction by low shear stress: pharmacological evaluation of the role of signaling molecules.
    Author: Cheng M, Liu X, Li Y, Tang R, Zhang W, Wu J, Li L, Liu X, Gang Y, Chen H.
    Journal: Biorheology; 2007; 44(5-6):349-60. PubMed ID: 18556829.
    Abstract:
    Shear stress can modulate endothelial cell function by regulating gene expression. We have previously demonstrated that low shear stress (4.2 dyn/cm(2)) 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/cm(2)) 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, GDPbetaS, 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 Ca(2+) chelator), Verapamil (a Ca(2+) 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.
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