Role of Toll‐like receptor 4/NF‐κB pathway in monocyte–endothelial adhesion induced by low shear stress and ox‐LDL

Abstract

TLR4 plays an important role in atherosclerosis, but little is known about the precise mechanism. Herein, we investigated the role of TLR4/NF‐κB signaling pathway in monocyte–endothelial adhesion induced by low shear stress and Ox‐LDL. We found that low shear stress up‐regulated TLR4 expression in endothelial cells, and that ox‐LDL exerted an obvious synergistic action as revealed by RT‐PCR and Western blotting analysis. Low shear stress also significantly up‐regulated IL‐8 expression in endothelial cells. Meanwhile, NF‐κB activity and the adhesion force of monocytes were increased, and there was a synergetic action of ox‐LDL. However, following transfection with a functional mutant of TLR4 (C3H/HeJ, TLR4 Dicd) or addition of anti‐human TLR4 mAb, IL‐8 expression was obviously decreased, NF‐κB activity in cells remarkably inhibited, and the adhesion force of monocyte significantly reduced. Nevertheless, anti‐human TLR2 mAb had no similar effects. These findings suggest that TLR4 may be involved in the early stages of atherosclerosis, associating ox‐LDL, inflammation/infection, and low shear stress. Therefore, TLR4 is expected to be a new target for preventing and treating atherosclerosis.