title: Se-methylselenocysteine inhibits lipopolysaccharide-induced NF-κB activation and iNOS induction in RAW 264.7 murine macrophages.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Seafood Science, National Kaohsiung Marine University, Nan-Tzu, Kaohsiung, Taiwan.
authors.forename: Min-Hsiung
authors.initials: MH
authors.lastname: Pan
authors.forename: Huei-Mei
authors.initials: HM
authors.lastname: Hong
authors.forename: Chih-Li
authors.initials: CL
authors.lastname: Lin
authors.forename: Ai-Zhi
authors.initials: AZ
authors.lastname: Jhang
authors.forename: Jie-Heng
authors.initials: JH
authors.lastname: Tsai
authors.forename: Vladimir
authors.initials: V
authors.lastname: Badmaev
authors.forename: Kalyanam
authors.initials: K
authors.lastname: Nagabhushanam
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004790:Enzyme Induction; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D017279:Selenocysteine / Q000031:analogs & derivatives
chemical_list: D016588:Anticarcinogenic Agents; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D016566:Organoselenium Compounds; D012333:RNA, Messenger; D017279:Selenocysteine; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D003545:Cysteine; C002979:selenomethylselenocysteine