Low shear stress-induced interleukin-8 mRNA expression in endothelial cells is mechanotransduced by integrins and the cytoskeleton

Shear stress is thought to be important in maintaining vascular homeostasis and regulating vascular remodeling. The authors have previously shown that low shear stress increases interleukin (IL)-8 gene expression in endothelial cells. However, the detailed events that contribute to the regulation of this expression remain to be identified. In this study, the authors examined whether the shear stress-induced IL-8 mRNA expression in endothelial cells is mechanotransduced by integrins and the cytoskeleton. Exposure of endothelial cells to low shear stress (4.2 dyne/cm(2)) rapidly increased the expression of IL-8 mRNA. The induced IL-8 mRNA expression was inhibited by GRGDNP, which blocked the binding of integrins to the extracellular matrix. Additionally, this increase was attenuated by both anti-alpha(upsilon)beta(3) integrin and anti-beta(1) integrin antibodies. Treatment of endothelial cells with either low shear stress or cytochalasin D resulted in the disruption of the cytoskeleton. Following the disruption of filamentous F-actin, the IL-8 mRNA expression in endothelial cells also increased, indicating that the shear stress-induced IL-8 mRNA expression may be mediated by the disruption of actin fibers. Taken together, these data suggest that integrins and the actin cytoskeleton play important roles in regulating the shear stress-induced IL-8 gene expression. Supplementary materials are available for the Materials and Methods section of this article. Go to the publisher's online of edition of Endothelium for this free supplemental resource.