Nicotinamide decreases cytokine-induced activation of orbital fibroblasts from patients with thyroid-associated ophthalmopathy.
We used flow cytometry to investigate the effects of nicotinamide, an inhibitor of poly (ADP ribose) synthetase, on the cell-surface expression of cytokine-induced human leukocyte antigen (HLA)-A,B,C antigen, HLA-DR antigen, intercellular adhesion molecule 1, CD44, and Fas expression in cultured orbital fibroblasts from patients with thyroid-associated ophthalmopathy. After two to seven passages, cultured orbital fibroblasts were incubated for 3 days with interferon gamma or tumor necrosis factor alpha in the presence of nicotinamide. Nicotinamide inhibited the induction of both HLA-DR and intercellular adhesion molecule 1 expression by cytokines on fibroblasts but did not interfere with induction of HLA-A,B,C, or CD44 expression. Nicotinamide also inhibited the proliferation of orbital fibroblasts, as assessed by a [3H]-thymidine incorporation assay and cell counts. Nicotinamide also enhanced the expression of the apoptosis-mediating protein Fas on fibroblasts. Our data suggest that nicotinamide inhibits cytokine-induced activation of fibroblasts and thus may decrease the autoimmune injury to the orbit in thyroid-associated ophthalmopathy.
Hiromatsu
Y
Y
Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Yang
D
D
Miyake
I
I
Koga
M
M
Kameo
J
J
Sato
M
M
Inoue
Y
Y
Nonaka
K
K
D000273:Adipose Tissue / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006111:Graves Disease / Q000276:immunology*; D015234:HLA-A Antigens / Q000096:biosynthesis; D015235:HLA-B Antigens / Q000096:biosynthesis; D015236:HLA-C Antigens / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D009536:Niacinamide / Q000494:pharmacology*; D009915:Orbit; D012867:Skin / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000096:biosynthesis
D016207:Cytokines; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D018960:Hyaluronan Receptors; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D018799:Intercellular Adhesion Molecule-1; D009536:Niacinamide; D007371:Interferon-gamma