Lipopolysaccharide and interferon‐γ enhance Fas‐mediated cell death in mouse vascular endothelial cells via augmentation of Fas expression

Summary The effect of interferon (IFN)‐γ and/or lipopolysaccharide (LPS) on Fas‐mediated cell death with anti‐Fas agonistic antibody in vascular endothelial cells was examined using a mouse END‐D cell line. Anti‐Fas agonistic antibody exhibited cytotoxic actions on END‐D cells. Fas‐mediated cell death was enhanced by LPS or IFN‐γ. The combination of IFN‐γ and LPS significantly enhanced cell death compared to IFN‐γ or LPS alone. IFN‐γ and LPS augmented cell surface expression of Fas, but not tumour necrosis factor (TNF) receptor 1. Inhibitors of p38 mitogen‐activated protein kinase (MAPK) prevented augmentation of Fas expression in IFN‐γ and LPS‐treated END‐D cells. IFN‐γ and LPS‐treated END‐D cells did not become susceptible to TNF‐α or nitric oxide‐mediated cytotoxicity. IFN‐γ and LPS thus appear to augment selectively Fas expression via activation of p38 MAPK and enhance Fas‐mediated cell death in END‐D cells. Furthermore, administration of IFN‐γ and LPS into mice induced in vivo expression of Fas on vascular endothelial cells and Fas ligand (FasL) on peripheral blood leucocytes. The relationship between enhancement of Fas‐mediated cell death by IFN‐γ and LPS and the development of vascular endothelial injury is discussed.