Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor αB through the repression of IKKα/β phosphorylation

Yusuke Ohsaki, Hitoshi Shirakawa, Akihito Miura, Puspo E. Giriwono, Shoko Sato, Ai Ohashi, Maiko Iribe, Tomoko Goto, Michio Komai

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)

Abstract

Vitamin K is essential for blood coagulation and bone metabolism in mammals. This vitamin functions as a cofactor in the posttranslational synthesis of γ-carboxyglutamic acid (Gla) from glutamic acid residues. However, other functions of vitamin K have been reported recently. We previously found that vitamin K suppresses the inflammatory reaction induced by lipopolysaccharide (LPS) in rats and human macrophage-like THP-1 cells. In this study, we further investigated the mechanism underlying the anti-inflammatory effect of vitamin K by using cultures of LPS-treated human- and mouse-derived cells. All the vitamin K analogues analyzed in our study exhibited varied levels of anti-inflammatory activity. The isoprenyl side chain structures, except geranylgeraniol, of these analogues did not show such activity; warfarin did not interfere with this activity. The results of our study suggest that the 2-methyl-1,4-naphtoquinone ring structure contributes to express the anti-inflammatory activity, which is independent of the Gla formation activity of vitamin K. Furthermore, menaquinone-4, a form of vitamin K2, reduced the activation of nuclear factor κB (NFκB) and inhibited the phosphorylation of IKKα/β after treatment of cells with LPS. These results clearly show that the anti-inflammatory activity of vitamin K is mediated via the inactivation of the NFκB signaling pathway.

Original languageEnglish
Pages (from-to)1120-1126
Number of pages7
JournalJournal of Nutritional Biochemistry
Volume21
Issue number11
DOIs
Publication statusPublished - 2010 Nov

Keywords

  • Anti-inflammation
  • IKK
  • Macrophage
  • Nuclear factor κB
  • Vitamin K

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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