Nicotinamide and 3-aminobenzamide inhibit recombinant human interferon-gamma-induced HLA-DR antigen expression, but not HLA-A, B, 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.


METHODS
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.
Hiromatsu
Y
Y
Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Sato
M
M
Yamada
K
K
Nonaka
K
K
D001549:Benzamides / Q000494:pharmacology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006111:Graves Disease / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D015236:HLA-C Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D009536:Niacinamide / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011994:Recombinant Proteins; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D001549:Benzamides; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011994:Recombinant Proteins; D009536:Niacinamide; D007371:Interferon-gamma; C025160:3-aminobenzamide