Gamble, Jennifer R.Bradley, SandyNoack, LeanneVadas, Mathew Alexander2006-07-052006-07-051995Arteriosclerosis, Thrombosis and Vascular Biology, 1995; 15(7):949-9551079-5642http://hdl.handle.net/2440/11526Vascular smooth muscle cells (VSMCs) are normally devoid of the adhesion protein vascular cell adhesion molecule–1 (VCAM-1), which has, however, been observed on human VSMCs in atheroma. We now show that cultured human saphenous vein VSMCs express small amounts of VCAM-1 and that the cytokine tumor necrosis factor–α (TNF-α) induces, in a time- and dose-dependent fashion, a significant increase in its expression. Interleukin (IL)-4, IL-1, and to a lesser extent interferon gamma have similar effects. TNF-α–stimulated human VSMCs demonstrate increased binding of T lymphocytes that is totally VCAM-1 mediated. The cytokine transforming growth factor–β (TGF-β) at 2.0 ng/mL inhibited basal VCAM-1 expression by 84±8% and the induction by TNF-α by between 56±16% and 77±15% depending on the dose of TNF. Furthermore, coculture on opposing sides of a polycarbonate filter of human VSMCs with human umbilical vein endothelial cells also inhibited the induction of VCAM-1 by 47±6%. As active TGF-β is produced upon the coculture of VSMCs and endothelial cells, we suggest that the close physical proximity of these cells in vivo is responsible for the lack of expression of VCAM-1 on VSMCs and that the interruption of this contact in atheroma is an important pathogenic event. As VCAM-1 not only serves as an adhesion molecule but also as a costimulator of immune cells, its expression may be crucial in the propagation of vascular lesions.enAtherogenesis; T cell adhesion; tumor necrosis factor; interleukin-4Journal article001995177810.1161/01.ATV.15.7.949