Nitric Oxide Synthase mRNA in Endothelial Cells: Synergistic Induction by Interferon-γ, Tumor Necrosis Factor-α and Lipopolysaccharide and Inhibition by Dexamethasone

The Japanese Journal of Pharmacology

Hiroko Adachi¹  Toshio Nakaki³  Takao Saruta²  Ryuichi Kato³  Takeshi Marumo³  Hiromichi Suzuki¹  Hiroyasu Esumi¹ 

[1] Biochemistry Division, National Cancer Center Research Institute;Departments of Internal Medicine, Keio University School of Medicine;Departments of Pharmacology, Keio University School of Medicine

关键词: Nitric oxide synthase mRNA;    Interferon-γ;    Tumor necrosis factor-α;    Dexamethasone;    Lipopolysaccharide;   

DOI  :  10.1254/jjp.63.327

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(34)Cited-By(8)Regulation of nitric oxide synthase mRNA by interferon-γ, tumor necrosis factor-α, bacterial lipopolysaccharide (LPS) and dexamethasone in rat aortic endothelial cells was examined. The combination of interferon-γ (100 U/ml) and tumor necrosis factor-α (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-γ (100 U/ml), tumor necrosis factor-α (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.

【 授权许可】

Unknown