Flavopiridol inhibits interferon-γ-induced nitric oxide production in mouse vascular endothelial cells.
Flavopiridol (FP), a synthetic flavone, is a cyclin-dependent kinase inhibitor and possesses an anti-cancer activity. The effect of FP on interferon (IFN)-γ-induced nitric oxide (NO) production in mouse vascular endothelial cell line END-D was examined. FP significantly inhibited IFN-γ-induced NO production in END-D cells via reduced expression of an inducible NO synthase. FP inhibited the activation of STAT1, and subsequently IRF1 as a downstream molecule of STAT1, which is essential for IFN-γ-induced NO production. FP did not affect the cell surface expression of IFN-γ receptor. Taken together, FP was suggested to inhibit IFN-γ-induced NO production in vascular endothelial cells via preventing intracellular IFN-γ signaling. FP might be useful as an immunomodulatory drug as well as an anti-cancer drug.
Departments of Emergency Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
Tsuguaki
T
Terashima
Abedul
A
Haque
Yuka
Y
Kajita
Akinori
A
Takeuchi
Takashi
T
Nakagawa
Takashi
T
Yokochi
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D042783:Endothelial Cells / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D056747:Immunomodulation; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D005419:Flavonoids; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D009569:Nitric Oxide; C077990:alvocidib; D007371:Interferon-gamma; D018844:Cyclin-Dependent Kinases