Se-methylselenocysteine inhibits lipopolysaccharide-induced NF-κB activation and iNOS induction in RAW 264.7 murine macrophages

Scope: Se-methyl-L-selenocysteine (MSC), a naturally occurring organoselenium compound, has shown cancer chemopreventive activity against several types of cancer. Herein, the effect of MSC on the inflammatory response in lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophage cells was investigated. Methods and results: The present results demonstrated that MSC markedly inhibited LPS-induced production of NO in a dose-dependent pattern with decreased mRNA and protein levels of inducible nitric oxide synthase (iNOS). MSC also reduced nuclear translocation of p65 and p50 subunits of nuclear factor-kappa B (NF-kappa B), a critical transcription factor necessary for iNOS expression, accompanied with downregulation of LPS-triggered NF-kappa B-dependent gene expression evaluating by a luciferase reporter. Inhibition of nuclear translocation by MSC might result from the prevention of the inhibitor of NF-kappa B from phosphorylation and consequent degradation via suppression inhibition of phosphorylation of I kappa B kinase alpha/beta. Exploring the action mechanism involved, MSC can reduce the phosphorylation/activation of mitogen-activated protein kinases (MAPKs) related to NF-kappa B activation induced by LPS, including p38 MAPK and c-Jun N-terminal kinase in RAW 264.7 cells. Conclusion: MSC might contribute to the potent anti-inflammatory effect in LPS-activated RAW 264.7 cells via downregulation of NF-kappa B activation and iNOS expression, suggesting that MSC may be considered as a therapeutic candidate for chronic inflammatory diseases.