NICOTINAMIDE AND 3-AMINOBENZAMIDE INHIBIT RECOMBINANT HUMAN INTERFERON-GAMMA-INDUCED HLA-DR ANTIGEN EXPRESSION, BUT NOT HLA-A, HLA-B, HLA-C ANTIGEN EXPRESSION, ON CULTURED HUMAN THYROID-CELLS

OBJECTIVE We wished to investigate the effects of nicotinamide and 3-aminobenzamide, well known as inhibitors of poly(ADP ribose) synthetase, on interferon-gamma-induced HLA-DR antigen expression using cultured human thyroid cells from patients with Graves' disease. DESIGN AND MEASUREMENTS Cultured thyroid cells were incubated for 3 days with 10-400 U/ml of interferon-gamma in the presence of nicotinamide, 3-aminobenzamide, superoxide dismutase or catalase. The surface expression of HLA-DR and HLA-A, B, C antigen was measured by flow cytometry. RESULTS Nicotinamide and 3-aminobenzamide dose-dependently inhibited the induction of HLA-DR antigen expression by interferon-gamma, but not HLA-A, B, C antigen expression on cultured thyroid cells. Neither catalase nor superoxide dismutase, which are free-radical scavengers, inhibited the expression of HLA antigens on thyroid cells. CONCLUSIONS Our data suggest that inhibitors of poly(ADP ribose) synthetase may have differential effects on interferon-gamma-induced HLA-DR and HLA-A, B, C antigen expression, and suppress the autoimmune reactions associated with autoimmune thyroid disorders via the reduction of HLA-DR antigen expression on thyroid cells. The mechanism of the suppression of HLA-DR antigen expression is unlikely to be due to the free radical scavenging.