Lipopolysaccharide enhances interferon-γ-induced nitric oxide (NO) production in murine vascular endothelial cells via augmentation of interferon regulatory factor-1 activation

Abstract

Lipopolysaccharide (LPS) enhances the production of nitric oxide (NO) in interferon (IFN)-γstimulated vascular endothelial cells. We studied the mechanism by which LPS enhances IFN-γ-induced NO production by using the murine vascular endothelial cell line, END-D. LPS enhanced IFN-γinduced NO production via augmented expression of inducible type NO synthase (iNOS) mRNA. LPS significantly augmented the activation of interferon regulatory factor (IRF)-1 in IFN-γ-stimulated END-D cells, although it did not affect the activation of either MyD88-dependent nuclear factor (NF)-κB or MyD88-independent IRF-3. SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK), prevented the nuclear translocation of IRF-1 in LPS and IFN-γ-stimulated END-D cells, and inhibited the iNOS expression and NO production in those cells. Therefore, it is proposed that LPS enhanced NO production in IFN-γ-stimulated END-D cells via augmenting p38 MAPKmediated IRF-1 activation.

Keywords

LPS interferon-γ nitric oxide vascular endothelial cell IRF-1

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