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 orb...

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Published in:The journal of clinical endocrinology and metabolism 1998-01, Vol.83 (1), p.121-124
Main Authors: Hiromatsu, Yuji, Yang, Damu, Miyake, Ikuyo, Koga, Mari, Kameo, Junko, Sato, Masayuki, Inoue, Yoichi, Nonaka, Kyohei
Format: Article
Language:English
Subjects:
Adipose Tissue - enzymology
Adipose Tissue - pathology
Biological and medical sciences
Cell Division - drug effects
Cells, Cultured
Cytokines - pharmacology
Endocrinopathies
fas Receptor - biosynthesis
Fibroblasts - drug effects
Fibroblasts - immunology
Fibroblasts - pathology
Graves Disease - immunology
Histocompatibility Antigens Class I - biosynthesis
HLA-A Antigens - biosynthesis
HLA-B Antigens - biosynthesis
HLA-C Antigens - biosynthesis
HLA-DR Antigens - biosynthesis
Humans
Hyaluronan Receptors - biosynthesis
Intercellular Adhesion Molecule-1 - biosynthesis
Interferon-gamma - pharmacology
Medical sciences
Niacinamide - pharmacology
Non tumoral diseases. Target tissue resistance. Benign neoplasms
Orbit
Skin - drug effects
Skin - immunology
Thyroid. Thyroid axis (diseases)
Tumor Necrosis Factor-alpha - pharmacology
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Summary: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 interferonγ or tumor necrosis factor α 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.
ISSN:0021-972X
1945-7197
DOI:10.1210/jcem.83.1.4478