Effects of tumor necrosis factor on the interferon‐γ‐induced major histocompatibility complex class II antigen expression by human endothelial cells

Abstract

Effects of tumor necrosis factor-a (TNF) and interferon-β (IFN-β) on the IFN-γ-induced major histocompatibility complex (MHC) class II expression on human umbilical vein endothelial (HUVE) cells are reported. TNF inhibited the induction of MHC class XI expression by IFN-γ markedly, when added before or simultaneously with IFN-γ. However, TNF added to the cells 24 h after IFN-γ enhanced the expression of MHC class II antigens. IFN-β inhibited the MHC class II expression irrespective of the time at which it was added to the cells. Addition of IFN-β, TNF, IFN-γ, and the combination of IFN-β and IFN-γ or TNF and IFN-γ, resulted in all cases in an enhanced MHC class I antigen expression. Antibodies directed against IFN-β reversed the inhibition of MHC class II expression by both TNF and IFN-β. The enhancing effect of TNF could not be inhibited by anti-IFN-β indicating that TNF mediates enhancement of IFN-γ-induced MHC class II expression via a pathway other than IFN-β. The role of TNF in the up-regulation as well as in the down-regulation of MHC class II expression in inflammatory processes is discussed.