Inhibition of cytokine-induced MHC class II but not class I molecule expression on mouse islet cells by niacinamide and 3-aminobenzamide.
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.
Yamada
K
K
Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Miyajima
E
E
Nonaka
K
K
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001685:Biological Factors / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D007515:Islets of Langerhans / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D009536:Niacinamide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001549:Benzamides; D001685:Biological Factors; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D014409:Tumor Necrosis Factor-alpha; D009536:Niacinamide; D007371:Interferon-gamma; C025160:3-aminobenzamide