Flavopiridol inhibits interferon-gamma-induced nitric oxide production in mouse vascular endothelial cells

作者：Terashima Tsuguaki; Hague Abedul; Kajita Yuka; Takeuchi Akinori; Nakagawa Takashi; Yokochi Takashi^*

来源：Immunology Letters, 2012, 148(2): 91-96.

DOI：10.1016/j.imlet.2012.10.004

• Flavopiridol (FP)
• Nitric oxide (NO)
• Inducible NO synthase (iNOS)
• Interferon-gamma (IFN-gamma)
• Vascular endothelial cells
• Signal transducer and activator of transcription 1 (STAT1)

Flavopiridol (FP), a synthetic flavone, is a cyclin-dependent kinase inhibitor and possesses an anti-cancer activity. The effect of FP on interferon (IFN)-gamma-induced nitric oxide (NO) production in mouse vascular endothelial cell line END-D was examined. FP significantly inhibited IFN-gamma-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-gamma-induced NO production. FP did not affect the cell surface expression of IFN-gamma receptor. Taken together, FP was suggested to inhibit IFN-gamma-induced NO production in vascular endothelial cells via preventing intracellular IFN-gamma signaling. FP might be useful as an immunomodulatory drug as well as an anti-cancer drug.

• 出版日期2012-12