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

Abstract

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.