NICOTINAMIDE AND 3-AMINOBENZAMIDE REDUCE INTERFERON-GAMMA-INDUCED CLASS-II MHC (HLA-DR AND HLA-DP) MOLECULE EXPRESSION ON CULTURED HUMAN ENDOTHELIAL-CELLS AND FIBROBLASTS

We investigated the effects of nicotinamide and 3-aminobenzamide, known as inhibitors of poly(ADP-ribose) synthetase, on the expression of interferon-gamma (IFN-gamma)-induced class I and II major histocompatibility complex (MHC) molecules on the surface of cultured human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF). Indirect immunofluorescent staining on HUVEC and HDF was performed using monoclonal antibodies against class I MHC (HLA-A,B,C) and class II MHC (HLA-DR, HLA-DP and HLA-DQ) molecules, and then the expression of these molecules was determined using a fluorescence flow cytometry. Human recombinant IFN-gamma (100 U/ml) increased the expression of HLA-A,B,C molecules, and induced the expression of HLA-DR molecules and, to a lesser extent, of HLA-DP on both HUVEC and HDF. HLA-DQ molecules were not induced by IFN-gamma on either cell type. Nicotinamide and 3-aminobenzamide in the concentration greater than or equal to 1 mM reduced the IFN-gamma-induced expression of HLA-DR and HLA-DP on both HUVEC and HDF, whereas neither agent in the concentration of up to 10 mM affected the IFN-gamma-induced increase in HLA-A,B,C molecule expression. These data suggest that nicotinamide and 3-aminobenzamide suppress antigen presenting function of class II MHC positive endothelial cells and fibroblasts at the site of tissue inflammation.