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

• Published in: The Journal of nutritional biochemistry Vol. 21; no. 11; pp. 1120 - 1126
• Main Authors: Ohsaki, Yusuke, Shirakawa, Hitoshi, Miura, Akihito, Giriwono, Puspo E., Sato, Shoko, Ohashi, Ai, Iribe, Maiko, Goto, Tomoko, Komai, Michio
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2010; New York, NY: Elsevier Science; Elsevier
• Subjects: 1-Carboxyglutamic Acid - metabolism; Animals; Anti-inflammation; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Blotting, Western; Cell Line; Cytokines - metabolism; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Humans; I-kappa B Kinase - metabolism; IKK; Interleukin-6 - metabolism; Lipopolysaccharides - adverse effects; Lipopolysaccharides - metabolism; Macrophage; Mice; Mice, Inbred C57BL; NF-kappa B - metabolism; Nuclear factor κB; Phosphorylation; RNA, Messenger - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin K; Vitamin K - metabolism; Vitamin K - pharmacology; IKK; Anti-inflammation; Macrophage; Nuclear factor κB; Vitamin K; Phosphorylation; B; Nuclear factor; Cytokine; Activation; Inflammation; Gene expression; In vitro; Vertebrata; Mammalia; Lipopolysaccharide; Transcription factor NFκB; Inhibition
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2009.09.011

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 K 2, 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.