Inhibitory effects of nicotinamide on recombinant human interferon-gamma-induced intercellular adhesion molecule-1 (ICAM-1) and HLA-DR antigen expression on cultured human endothelial cells.
Intercellular adhesion molecule-1 (ICAM-1), HLA-A, B, C and HLA-DR antigen on endothelial cells (EC) play important roles in the development of inflammatory processes in autoimmune disorders. In the present study, we investigated the effect of nicotinamide, an inhibitor of poly(ADP ribose) synthetase, on interferon-gamma (IFN gamma)-induced ICAM-1 and HLA-DR antigen expression on the surface of cultured human umbilical vein endothelial cells, assessed by flow cytometry, and EC proliferation by counting cell numbers and [3H]thymidine incorporation assays. Nicotinamide dose-dependently inhibited the IFN-gamma-induced ICAM-1 and HLA-DR antigen expression, but not HLA-A, B, C antigen expression on cultured EC. Furthermore, nicotinamide significantly inhibited endothelial cell proliferation, as assessed by [3H]thymidine incorporation assay. Our findings suggest that nicotinamide may suppress mononuclear cell infiltration, antigen presentation and angiogenesis in the lesions of autoimmune disorders by reducing both IFN gamma-induced ICAM-1 and HLA-DR antigen expression on EC, and EC proliferation. Therefore, nicotinamide can be used for the treatment and prevention of the development of autoimmune disorders.
Hiromatsu
Y
Y
Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Sato
M
M
Yamada
K
K
Nonaka
K
K
D015703:Antigens, CD / Q000187:drug effects / Q000235:genetics; D000954:Antigens, Surface / Q000187:drug effects / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005786:Gene Expression Regulation; D015234:HLA-A Antigens / Q000187:drug effects / Q000235:genetics; D015235:HLA-B Antigens / Q000187:drug effects / Q000235:genetics; D015236:HLA-C Antigens / Q000187:drug effects / Q000235:genetics; D006684:HLA-DR Antigens / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology*; D009536:Niacinamide / Q000494:pharmacology*; D014470:Umbilical Cord / Q000166:cytology
D015703:Antigens, CD; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1; D009536:Niacinamide; D007371:Interferon-gamma