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)-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. (C) 2012 Elsevier B.V. All rights reserved.