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

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