title: NF-kappaB signaling pathway, not IFN-beta/STAT1, is responsible for the selenium suppression of LPS-induced nitric oxide production.
abstract: Upon stimulation of macrophages with lipopolysaccharide (LPS), Toll-like receptor 4 recognizes LPS, leading to expression of inducible nitric oxide synthase (iNOS), via MyD88/NF-kappaB and TRIF/IFN-beta/STAT pathways. Although selenium (Se) was reported to inhibit nitric oxide (NO) production, it is unclear which signaling pathway is inhibited by Se. Here, we investigated how Se inhibits NO production in LPS-stimulated RAW 264.7 cells. When the cells were pretreated with Se for 1 h followed by LPS treatment, iNOS mRNA expression and subsequent NO production declined significantly in a dose-dependent manner. Se inhibited IkappaBalpha degradation in the cytosol and NF-kappaB binding to its recognition site in the nucleus of the LPS-stimulated cells. Meanwhile, Se did not inhibit IFN-beta mRNA induction or STAT1 phosphorylation in the LPS-stimulated cells. These results suggest that Se down-regulates iNOS gene expression and NO production in the LPS-stimulated macrophages through inhibition of the NF-kappaB activation pathway but not the IFN-beta/STAT1 signaling pathway.
authors.affiliation: School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Yang
authors.forename: Seok-Seong
authors.initials: SS
authors.lastname: Kang
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.forename: Jung Hyo
authors.initials: JH
authors.lastname: Cho
authors.forename: Chang Gue
authors.initials: CG
authors.lastname: Son
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
mesh_terms: D000818:Animals; D002460:Cell Line; D016899:Interferon-beta / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D050794:STAT1 Transcription Factor / Q000502:physiology; D012643:Selenium / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D009569:Nitric Oxide; D016899:Interferon-beta; D012643:Selenium