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

Ohsaki, Yusuke; Shirakawa, Hitoshi; Miura, Akihito; Giriwono, Puspo Edi; Sato, Shoko; Ohashi, Ai; Iribe, Maiko; Gotō, Tomoko; Komai, Michio

doi:10.1016/j.jnutbio.2009.09.011

Cited by 135 publications

(136 citation statements)

References 35 publications

(34 reference statements)

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“…This study also found that supplementation with vitamin K1 also caused a rise in hepatic tissue menaquinone-4 levels [57]. Extension of these in vivo findings in the two cell lines, THP-1 and RAW264.7, demonstrated that the suppression of LPS-stimulated IL-6 mRNA by vitamin K2 was consistent with inhibition of NF-κB activity via the restricted phosphorylation of IKK kinases [58]. These researchers also questioned whether these events involved a classical vitamin K gammacarboxylation-mediated process; co-culture experiments with warfarin found that these inhibitory effects of vitamin K on NF-κB were independent of vitamin K-dependent protein gamma-carboxylation [58].…”

Section: Nf-κb and Vitamin Ksupporting

confidence: 64%

“…These include studies using germ-free rats, THP-1 human monocyte-like cells and murine RAW264.7 macrophage-like cells [57,58] and have noted a significant reduction in the LPS-stimulated cellular IL-6 mRNA levels. In the vitamin K supplemented animal experiments, there was a suppression of the hepatic mRNA levels of the inflammation response protein macrophage migration inhibitory factor (MIF), compared to animals fed a vitamin K-deficient diet.…”

Section: Nf-κb and Vitamin Kmentioning

confidence: 99%

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Anti-Inflammatory Actions of Vitamin K

Hodges¹,

Pitsillides²,

Ytrebø³

et al. 2017

Vitamin K2 - Vital for Health and Wellbeing

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Naphthoquinone compounds have received attention for their ability to regulate diseases from bacterial and parasite infections through to chronic human diseases. Inflammation is widely considered to be at the root of many chronic diseases. The reports of anti-inflammatory activity of naphthoquinones, including vitamin K1 (phylloquinone) and vitamin K2s (menaquinones), are of interest due to their very low toxicity. Most of the evidence for the anti-inflammatory mechanisms of vitamin K suggests a role in the inhibition of the cell signalling complex nuclear factor kappa-B (NF-κB).

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Section: Nf-κb and Vitamin Ksupporting

confidence: 64%

Section: Nf-κb and Vitamin Kmentioning

confidence: 99%

Anti-Inflammatory Actions of Vitamin K

Hodges¹,

Pitsillides²,

Ytrebø³

et al. 2017

Vitamin K2 - Vital for Health and Wellbeing

View full text Add to dashboard Cite

show abstract

“…These results suggest that vitamin K is involved in steroid production in the testis. To link these results with the antiinflammatory properties of vitamin K observed in the lipopolysaccharide (LPS)-induced models [5,6], we examined the effects of dietary vitamin K on steroidogenesis in LPSinduced rats [27]. We found that dietary vitamin K intake affected testicular vitamin K concentration and offset the LPS-induced lowering of testosterone synthesis in the testis.…”

Section: Mk-4 Enhances Steroidogenesis By Activating Pkamentioning

confidence: 99%

“…Vitamin K is a well-known nutrient required for blood coagulation and bone metabolism. In recent years, novel functions of vitamin K against inflammation [5,6], tumors [7][8][9], and ligand of the nuclear receptor PXR (also known as SXR) [10,11] have been reported. These findings suggest the beneficial role of vitamin K, including MK-4, in several biological processes.…”

Section: Introductionmentioning

confidence: 99%

Menaquinone‐4 Enhances Steroidogenesis in Testis Derived Tumor Cells Via the Elevation of cAMP Level

Ho¹,

Shirakawa²,

Komai³

2017

Vitamin K2 - Vital for Health and Wellbeing

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Naturally existing vitamin K consists of vitamins K1 and K2. Menaquinone-4 (MK-4), an analog of vitamin K2 and a product of vitamin K1 metabolism, can be detected in several organs, including the testis; however, the function of MK-4 in these tissues has not been well characterized. Recent studies have suggested that vitamin K is involved in enhancing protein kinase A (PKA) activity in several cell types, thus regulating numerous PKA-dependent biological processes. To highlight the effect of vitamin K, we focused on its role in the steroidogenic pathway. Experiments on vitamin K-deficient rats revealed a reduced expression of genes involved in the biosynthesis of cholesterol and steroid hormones in the testis. Moreover, compared with control animals, rats fed on MK-4 diet presented significantly higher testosterone levels in the plasma and testis. These results suggest that vitamin K is involved in the steroidogenic pathway in the testis. Testosterone levels were found to increase in a dose-dependent manner also in cell-based experiments upon addition of MK-4, but such an effect was not observed in vitamin K1 levels. Furthermore, the effect of MK-4 on testosterone production was abolished by the specific PKA inhibitor H89, thus confirming the regulatory role of MK-4 on PKA activation. Here, we describe how MK-4 modulates PKA activation by enhancing intracellular 3′,5′-cyclic adenosine monophosphate (cAMP) levels in testisderived I-10 cells. The presented evidence supports the role of MK-4 in cAMP/PKA signaling and steroidogenesis.

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“…The use of vitamin K antagonists (VKAs) such as warfarin, known to influence the carboxylation of Glu residues of the coagulation factors in liver, has been shown to also impair the γ-carboxylation of extra-hepatic VKDPs, resulting in unwanted pathological side-effects in tissues such as bone and blood vessels [6,7,[9][10][11][12]. Recently, additional functions of vitamin K, such as anti-inflammatory, transcriptional regulator of osteoblastic genes, and inhibition of tumor progression, have been proposed to be mediated by a direct vitamin K effect rather than through VKDPs action [13,14]. However, the function of VKDPs associated to these emerging functions of vitamin K has been poorly explored.…”

Section: Introductionmentioning

confidence: 99%

New Perspectives for the Nutritional Value of Vitamin K in Human Health

Viegas¹,

Simes²

2016

J Nutr Disorders Ther

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Vitamin K is an essential micronutrient in the post-translational modification of specific glutamic acid residues (Glu) into γ-carboxyglutamic acid residues (Gla) in target proteins known as vitamin K-dependent proteins (VKDPs). In healthy conditions of sufficient vitamin K status, a vitamin K recycling system maintains sufficient vitamin K levels for proper γ-carboxylation of VKDPs, and vitamin K antagonists (VKAs) widely used as anticoagulants inhibit vitamin K recycling. Besides its well-known function in the maintenance of normal coagulation, vitamin K has been reported to have other diverse physiological functions with impact in human health. In extra-hepatic tissues vitamin K deficiency results in impairment of VKDPs γ-carboxylation with important implications in bone and cardiovascular health. Although most of the vitamin K effects have been associated with regulation of mineralization in connective tissues through the action of matrix Gla protein (MGP) and osteocalcin (OC), the discovery of Gla-rich protein (GRP) opens new perspectives on the potential therapeutic range of vitamin K.

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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

Cited by 135 publications

References 35 publications

Anti-Inflammatory Actions of Vitamin K

Anti-Inflammatory Actions of Vitamin K

Menaquinone‐4 Enhances Steroidogenesis in Testis Derived Tumor Cells Via the Elevation of cAMP Level

New Perspectives for the Nutritional Value of Vitamin K in Human Health

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