Inhibitory Effect of an Urotensin II Receptor Antagonist on Proinflammatory Activation Induced by Urotensin II in Human Vascular Endothelial Cells

摘要

In this study, we investigated the effects of a selective urotensin II (Ull) receptor antagonist, SB-657510, on the inflammatory response induced by Ull in human umbilical vein endothelial cells (EA.hy926) and human monocytes (U937). Ull induced inflammatory activation of endothelial cells through expression of proinflammatory cytokines (IL-ip and IL-6), adhesion molecules (VCAM-1), and tissue factor (TF), which facilitates the adhesion of monocytes to EA.hy926 cells. Treatment with SB-657510 significantly inhibited UN-induced expression of IL-ip, IL-6, and VCAM-1 in EA.hy926 cells. Further, SB-657510 dramatically blocked the Ull-induced increase in adhesion between U937 and EA.hy926 cells. In addition, SB-657510 remarkably reduced UN-induced expression of TF in EA.hy926 cells. Taken together, our results demonstrate that the Ull antagonist SB-657510 decreases the progression of inflammation induced by Ull in endothelial cells.