Differential Regulation of Constitutive and Inducible Nitric Oxide Production by Inflammatory Stimuli in Murine Endothelial Cells

Abstract

The murine vascular endothelial cell line send1 expresses both constitutive and inducible nitric oxide (NO) synthases. Interferon-gamma (IFNγ) or endotoxin (LPS) alone inhibited constitutive NO production in a dose and time dependent manner. Addition of L-arginine had no influence on the decrease of NO production caused by IFNγ or LPS. On the other hand, IFNγ and LPS synergized in the induction of high output NO production. Successive incubations with IFNγ and LPS in different sequences revealed IFNγ as the time setting signal for the induction of NO synthesis. These results demonstrate that LPS and IFNγ have a direct suppressive effect on constitutive NO synthase while at the same time they strongly activate inducible NO production. Thus inflammatory stimuli trigger murine vascular endothelial cells to switch from constitutive to inducible NO synthase activity.