Interferon-gamma stimulates the expression of CX3CL1/fractalkine in cultured human endothelial cells

CX3CL1/Fractalkine, a CX3C chemokine, is a potent agonist for the chemotaxis and adhesion of monocytes and lymphocytes. It was first identified as a membrane protein in endothelial cells activated with IL-1 or TNF-alpha. We have found the enhanced expression of fractalkine in human umbilical vein endothelial cells stimulated with interferon-gamma (IFN-gamma). Pretreatment of the cells with cycloheximide did not inhibit the expression of fractalkine mRNA. The majority of fractalkine protein was found in the cell lysate, and an antibody-blocking experiment disclosed that fractalkine contributes to the adhesion of mononuclear cells to endothelial monolayers stimulated with IFN-gamma. Vascular endothelial cells produce fractalkine in response to IFN-gamma, and this may play an important role in immune responses by eliciting a traffic of mononuclear cells through the vascular wall.