CD40 expression and function on human dermal microvascular endothelial cells: role in cutaneous inflammation

CD40 is a member of the tumour necrosis factor (TNF) cell surface receptor family. It plays an important role in T-cell dependent B-cell functions and in dendritic cell development. It has also been identified as a cell surface receptor on endothelial cells. In this manuscript, we report that human dermal microvascular endothelial cells (HDMEC) express cell surface CD40 and that the expression of CD40 is increased by the proinflammatory cytokines TNF-alpha and interferon (IFN)-gamma. Additionally, we demonstrate that engagement of HDMEC CD40 with its recombinant CD40 ligand augments the induction of E-selectin, but not of intercellular or vascular cell adhesion molecules on the surface of HDMEC. Furthermore, we show that IFN gamma stimulation of HDMEC results in increased binding of Jurkat leucocytes to HDMEC by a CD40--CD154 dependent pathway. This study thus provides evidence that CD40 expression in HDMEC is regulated by proinflammatory cytokines, and that CD40 functions as an important mediator of cutaneous inflammation.