Artemisinin inhibits lipopolysaccharide-induced nitric oxide production by blocking IFN-β production and STAT-1 signaling in macrophages (142.2)

Abstract

Abstract Artemisinin is a well-known anti-malarial drug and has been reported to exert anti-inflammatory and anti-tumor effects. In this study, we investigated the effect of artemisinin on lipopolysaccharide (LPS)-induced NO production in macrophages and the molecular mechanisms responsible for its effects. Artemisinin significantly suppressed NO production and inducible nitric oxide synthase (iNOS) mRNA expression in LPS-stimulated macrophages. NF-κB activity, which is known to be important for NO production and iNOS expression, was minimally inhibited only by highest concentration of artemisinin used and MAPKs were not affected by artemisinin treatment. In contrast, LPS-induced activation of STAT-1 was suppressed by artemisinin treatment in a concentration-dependent manner. Further studies demonstrated that the inhibition of STAT-1 activation by artemisinin might be mediated by blocking interferon-β (IFN-β) production. These results suggest that artemisinin suppresses NO production and iNOS expression, at least in part, by blocking IFN-β production and concomitant down-regulation of STAT-1 signaling.