Inflammatory modulation of vascular endothelium by fas ligand and TRAIL

Diseases like stroke or multiple sclerosis are worsened by the body's own immune responses, including the actions of white blood cells. White cells damage normal tissues only after binding to endothelial cells and crossing blood vessels to enter the tissue. This process is promoted by soluble factors called cytokines through a process called endothelial activation. Cytokines also increase the leakiness of blood vessels, known as permeability. Tumor necrosis factor is such a cytokine, and Fas ligand and TRAIL are closely related proteins, whose role in endothelial activation is presently unclear. We show that Fas ligand promotes endothelial activation while TRAIL inhibits it. Specifically, Fas ligand increases white cell adhesion and permeability, while TRAIL reduces permeability without promoting adhesion. We intend to confirm this observation in endothelial cells from the brain, and elsewhere, and explore the receptor signaling that mediates these effects. If TRAIL reduces inflammation, it may have an exciting therapeutic potential.