TGT-β and endothelial cells inhibit VCAM-1 expression on human vascular smooth muscle cells

dc.contributor.authorGamble, Jennifer R.en
dc.contributor.authorBradley, Sandyen
dc.contributor.authorNoack, Leanneen
dc.contributor.authorVadas, Mathew Alexanderen
dc.date.issued1995en
dc.description.abstractVascular 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.en
dc.description.statementofresponsibilityJennifer R. Gamble, Sandy Bradley, Leanne Noack, and Mathew A. Vadasen
dc.identifier.citationArteriosclerosis, Thrombosis and Vascular Biology, 1995; 15(7):949-955en
dc.identifier.doi10.1161/01.ATV.15.7.949en
dc.identifier.issn1079-5642en
dc.identifier.urihttp://hdl.handle.net/2440/11526
dc.language.isoenen
dc.publisherAmerican Heart Associationen
dc.subjectAtherogenesis; T cell adhesion; tumor necrosis factor; interleukin-4en
dc.titleTGT-β and endothelial cells inhibit VCAM-1 expression on human vascular smooth muscle cellsen
dc.title.alternativeTGT-beta and endothelial cells inhibit VCAM-1 expression on human vascular smooth muscle cellsen
dc.typeJournal articleen

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