Methylene Blue Attenuates iNOS Induction Through Suppression of Transcriptional Factor Binding Amid iNOS mRNA Transcription
Abstract
Inducible nitric oxide synthase (iNOS) critically contributes to the development of endotoxin-mediated inflammation. It can be induced by cytokines or endotoxins via distinct signaling pathways. Lipopolysaccharide (LPS) triggers iNOS expression through activation of the inhibitor of κB-α (IκB-α)-nuclear factor κB (NF-κB) cascade, whereas interferon-γ (IFN-γ) acts primarily through Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1). Methylene blue (MB), an agent used clinically to treat numerous ailments, has been shown to reduce NO accumulation through suppression of iNOS activity. But it remains unclear whether MB affects iNOS induction. This knowledge gap is addressed in the present study using cultured cells and endotoxemic mice. With mouse macrophages, MB treatment prevented the LPS- and/or IFN-γ-stimulated iNOS protein expression. Real-time PCR experiments showed that iNOS mRNA transcription was robustly blocked by MB treatment. The inhibitory effect of MB on iNOS expression was confirmed in vivo in endotoxemic mice. Further analysis showed that MB had no significant effect on IκB-α degradation and NF-κB or STAT1 phosphorylation in LPS/IFN-γ-stimulated cells. The nuclear transport of active NF-κB...Continue Reading
References
Inhibition of inducible nitric oxide synthase attenuates acute endotoxin-induced lung injury in rats
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