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Vitamin K modulates lipopolysaccharide‐induced expression of Interleukin (IL)‐6 through inactivation of NF‐κB
Author(s) -
Fu Xueyan,
Wu Dayong,
Meydani Simin N,
Booth Sarah L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.348.6
Subject(s) - proinflammatory cytokine , lipopolysaccharide , chemistry , nf κb , tumor necrosis factor alpha , cytokine , interleukin , endocrinology , iκbα , medicine , microbiology and biotechnology , inflammation , signal transduction , biology , biochemistry
Vitamin K (VK) status is inversely associated with circulating proinflammatory markers but the mechanism is not known. In this current study, we performed an in vitro study to determine if VK suppress LPS‐induced inflammatory cytokines in mice peritoneal macrophage (Mø). Male (3, 21 and 33 mo, n=9–12 per group) and female C57BL6 mice (3 mo, n=12) were injected with 2.98% thioglycollate into peritoneum to elicit Mø. Harvested Mø were incubated with phylloquinone (VK1) or menaquinone‐4 (MK‐4) at different doses for 24h, and then stimulated with 0.1μg/ml lipopolysaccharide (LPS) for 24 h. IL‐6 and TNF‐α concentration in medium were measured. To determine if VK inhibits translocation of NF‐κB into nucleus, RAW Mø were incubated with 10μM VK1 or MK‐4 for 24h, and then stimulated by LPS at 1μg/ml for 0, 15, 30 and 60 min. NF‐κB /p65, IκB‐α and IKK‐β protein levels were measured.VK1and MK‐4 suppressed LPS‐induced expression of IL‐6, but not TNF‐α, in a dose‐dependent manner. Warfarin, a VK antagonist, had no effects, suggesting that VK suppress IL‐6 expression via a mechanism unrelated to its role as enzyme‐cofactor. The p‐IKK and p‐NF‐κB /p65 protein levels were significantly lower in both VK1 and MK‐4 treatments. The inhibitory effect of VK on proinflammatory cytokine production maybe mediated through the NF‐κB pathway.