DIFFERENTIAL EFFECTS OF SHEAR STRESS ON THE EXPRESSIONS OF ICAM-1 AND VCAM-1 INDUCED BY TNF-α IN ENDOTHELIAL CELLS

Abstract

Vascular endothelial cells (ECs) are subjected to shear stress and cytokine stimulation. We studied the interplay between shear stress and cytokine in modulating the expression of adhesion molecule genes and the adhesive function of ECs. Shear stress (20 dynes/cm2) was applied to ECs prior to or following the addition of tumor necrosis factor (TNF)-α. Shear stress increased the TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1) at both mRNA and surface protein levels, but decreased the TNF-α-induced expression of vascular adhesion molecule-1 (VCAM-1). The TNF-α-induced increase in EC adhesiveness for monocytic THP-1 cells was reduced by shear stress. After 24-h pre-shearing followed by 1 h of static incubation, the effect of pre-shearing on TNF-α-induced ICAM-1 mRNA expression vanished. The recovery of the TNF-α-induced VCAM-1 mRNA expression following pre-shearing, however, required a static incubation time of >6 h (completely recovery at 24 h). Pre- and post-shearing caused a reduction in the nuclear factor (NF)-κB-DNA binding activity induced by TNF-α in the EC nucleus. Our findings suggest that shear stress plays differential roles in modulating the TNF-α-induced EC expressions of ICAM-1 and VCAM-1 genes, which serve similar functions in vascular biology.