Open AccessNitric Oxide Synthase mRNA in Endothelial Cells: Synergistic Induction by Interferon-γ, Tumor Necrosis Factor-α and Lipopolysaccharide and Inhibition by Dexamethasone
Author(s) -
Takeshi Marumo,
Toshio Nakaki,
H. Adachi,
Hiroyasu Esumi,
Hiromichi Suzuki,
Takao Saruta,
Ryuichi Kato
Publication year - 1993
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.63.327
Subject(s) - lipopolysaccharide , tumor necrosis factor alpha , dexamethasone , nitric oxide synthase , nitric oxide , chemistry , interferon , tumor necrosis factor α , messenger rna , pharmacology , microbiology and biotechnology , immunology , medicine , biology , endocrinology , biochemistry , gene , organic chemistry
Regulation of nitric oxide synthase mRNA by interferon-gamma, tumor necrosis factor-alpha, bacterial lipopolysaccharide (LPS) and dexamethasone in rat aortic endothelial cells was examined. The combination of interferon-gamma (100 U/ml) and tumor necrosis factor-alpha (5000 U/ml) evoked a time-dependent increase in nitric oxide synthase mRNA and nitrite/nitrate production, both of which were inhibited by dexamethasone. Neither interferon-gamma (100 U/ml), tumor necrosis factor-alpha (5000 U/ml) nor LPS (100 ng/ml) alone was capable of increasing nitric oxide synthase mRNA and nitrite/nitrate production in these cells. However, combinations of two of the three agents synergistically increased both nitric oxide synthase mRNA and nitrite/nitrate production. When the three agents were applied simultaneously, nitric oxide synthase mRNA and nitrite/nitrate production were both markedly increased. LPS contamination, which may affect the induction of nitric oxide synthase, was below 20 pg/ml in all experiments unless LPS was added exogenously, namely, the effects observed were those of the cytokines themselves. Our results suggest that in endothelial cells, these cytokines regulate the production of nitric oxide at the level of nitric oxide synthase mRNA induction.