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

Abstract

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-κB (NF-κB), a critical transcription factor necessary for iNOS expression, accompanied with downregulation of LPS-triggered NF-κB-dependent gene expression evaluating by a luciferase reporter. Inhibition of nuclear translocation by MSC might result from the prevention of the inhibitor of NF-κB from phosphorylation and consequent degradation via suppression inhibition of phosphorylation of IκB kinase α/β. Exploring the action mechanism involved, MSC can reduce the phosphorylation/activation of mitogen-activated protein kinases (MAPKs) related to NF-κB 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-κB activation and iNOS expression, suggesting that MSC may be considered as a therapeutic candidate for chronic inflammatory diseases.

• Authors: Min-Hsiung Pan, Huei-Mei Hong, Chih-Li Lin, Ai-Zhi Jhang, Jie-Heng Tsai, Vladimir Badmaev, Kalyanam Nagabhushanam, Chi-Tang Ho, Wei-Jen Chen
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 55 Issue 5 Pg. 723-32 (May 2011) ISSN: 1613-4133 [Electronic] Germany
• PMID: 21213327 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Anticarcinogenic Agents
• I-kappa B Proteins
• Lipopolysaccharides
• NF-kappa B
• Nfkbia protein, mouse
• Organoselenium Compounds
• RNA, Messenger
• Selenocysteine
• NF-KappaB Inhibitor alpha
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Mitogen-Activated Protein Kinases
• Cysteine
• selenomethylselenocysteine

Topics

• Animals
• Anticarcinogenic Agents (pharmacology)
• Cells, Cultured
• Cysteine (analogs & derivatives, pharmacology)
• Enzyme Induction
• I-kappa B Proteins (metabolism)
• Lipopolysaccharides (antagonists & inhibitors)
• Macrophages (drug effects, metabolism)
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• NF-KappaB Inhibitor alpha
• NF-kappa B (analysis, metabolism)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase Type II (biosynthesis, genetics)
• Organoselenium Compounds (pharmacology)
• Phosphorylation
• RNA, Messenger (analysis)
• Selenocysteine (analogs & derivatives)