Inhibition of cytokine-induced MHC class II but not class I molecule expression on mouse islet cells by niacinamide and 3-aminobenzamide

Abstract

Normal mouse islet cells express low levels of MHC class I molecules and undetectable or extremely low levels of MHC class II molecules. Class I expression was dose-dependently augmented by incubation with interferon-gamma (IFN-gamma) or tumor necrosis factor (TNF). Although neither IFN-gamma nor TNF alone induce class II molecules on islet cells, synergistic interaction of IFN-gamma (200 U/ml) and TNF (200 U/ml) may induce class II expression on approximately 50% of islet cells. Niacinamide and 3-aminobenzamide, both inhibitors of ADP ribosylation and scavengers of free radicals, attenuated the class II expression induced by IFN-gamma and TNF. Twenty millimolar niacinamide and 10 mM 3-aminobenzamide reduced the rates of class II antigen-positive cells to mean +/- SD 3.6 +/- 0.3 and 6.1 +/- 1.9%, respectively. The agents did not affect the cytokine-induced augmentation of class I antigens. The inhibition of class II molecule expression may at least partly account for the preventive effect of niacinamide on autoimmune-associated beta-cell damage in NOD mice.