Vitamin K1 and Vitamin K2 immunopharmacological effects on the peripheral lymphocytes of healthy subjects and dialysis patients, as estimated by the lymphocyte immunosuppressant sensitivity test

Kusano, Junichi; Tanaka, Sachiko; Matsuda, Hiroto; Hara, Yoshikazu; Fujii, Yoshiaki; Suzuki, Shinya; Sekiyama, Masao; Ando, Eiki; Sugiyama, Kentaro; Hirano, Toshihiko

doi:10.1111/jcpt.12747

Cited by 10 publications

(12 citation statements)

References 20 publications

(76 reference statements)

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“…Our previous studies highlighted the immunosuppressive effects of vitamins K2 and K3 (Hatanaka et al, 2014;Kusano et al, 2018;Meng et al, 2018;Xu, Meng, Wu, et al, 2019). In the present study, we compared the cytotoxic effects of vitamins K1, K2, and K3 on viabilities of T-cell mitogen-activated PBMCs (Figure 9 and Table 1).…”

Section: Discussionmentioning

confidence: 88%

Cytotoxic effects of vitamins K1, K2, and K3 against human T lymphoblastoid leukemia cells through apoptosis induction and cell cycle arrest

Chen

et al. 2020

Chem Biol Drug Des

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The present study was undertaken to evaluate cytotoxic effects of vitamin K1 (phylloquinone), vitamin K2 (menaquinones), and vitamin K3 (menadione) against human T lymphoblastoid leukemia cells, Jurkat T cells, MOLT‐4 cells, and P‐glycoprotein‐expressing multidrug‐resistant MOLT‐4/DNR cells. Vitamins K2 and K3, but not vitamin K1, reduced viabilities of Jurkat, MOLT‐4, and MOLT‐4/DNR cells. The influence potency of vitamin K3 was larger than that of vitamin K2 in all of the three cell lines. MOLT‐4/DNR cells seemed to be more sensitive toward the effects of vitamins K2 and K3. The cytotoxicity of vitamins K2 and K3 on these leukemia cells seems to be related to apoptosis induction and cell cycle arrest. Vitamin K2 and K3 treatment induced cleavage of PARP obviously. Moreover, vitamins K2 and K3 specifically down‐regulated the expressions of cyclin A2 in all of the three cell lines. However, the effects of vitamins K2 and K3 on the cell cycle profiling in Jurkat, MOLT‐4, and MOLT‐4/DNR cells varied with the cell type. Vitamins K2 and K3 also decreased the viability of mitogen‐activated human peripheral blood mononuclear cells. Our observations suggest that vitamins K2 and K3 have bilateral cytotoxic effects on activated human peripheral lymphocytes and the human leukemic T cells.

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Section: Discussionmentioning

confidence: 88%

Cytotoxic effects of vitamins K1, K2, and K3 against human T lymphoblastoid leukemia cells through apoptosis induction and cell cycle arrest

Chen

et al. 2020

Chem Biol Drug Des

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“…Furthering this finding, K2 decreases proliferation of T-cells from healthy individuals, whereas vitamin K1 had no such effect [ 103 ]. This has been further substantiated with T-cells from a larger number of children with pediatric atopic dermatitis and healthy controls, as well as a separate study with patients on dialysis [ 104 , 105 ]. Both these studies demonstrated that K2 decreased the number of activated T-cells, as well as proliferation.…”

Section: Vitamin K2 In Health and Diseasementioning

confidence: 91%

Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease

Halder

Petsophonsakul

Akbulut

et al. 2019

IJMS

177

140

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Vitamin K is an essential bioactive compound required for optimal body function. Vitamin K can be present in various isoforms, distinguishable by two main structures, namely, phylloquinone (K1) and menaquinones (K2). The difference in structure between K1 and K2 is seen in different absorption rates, tissue distribution, and bioavailability. Although differing in structure, both act as cofactor for the enzyme gamma-glutamylcarboxylase, encompassing both hepatic and extrahepatic activity. Only carboxylated proteins are active and promote a health profile like hemostasis. Furthermore, vitamin K2 in the form of MK-7 has been shown to be a bioactive compound in regulating osteoporosis, atherosclerosis, cancer and inflammatory diseases without risk of negative side effects or overdosing. This review is the first to highlight differences between isoforms vitamin K1 and K2 by means of source, function, and extrahepatic activity.

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“…The data were analyzed with FACSCanto II (BD Biosciences), using BD FACSDiva software. CD4 + T cells in the lymphocyte fraction were gated, and the percentages of CD4 + CD25 + and CD4 + CD25 + Foxp3 + cells in the CD4 + cell fraction were calculated, respectively, as we described previously (Kusano et al, 2018; Meng et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

Effects of sinomenine on the proliferation, cytokine production, and regulatory T‐cell frequency in peripheral blood mononuclear cells of rheumatoid arthritis patients

Chen

Wang

et al. 2020

Drug Development Research

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Sinomenine (SN) is a plant‐derived alkaloid isolated from Caulis Sinomenii. It has been approved by the State Food and Drug Administration of China for treating rheumatoid arthritis (RA) nearly 20 years ago. To investigate the anti‐RA mechanism of SN, a lot of scholars reported the immunosuppressive effect of SN on T lymphocytes. We continued to evaluate the suppressive function of SN by using human peripheral blood mononuclear cells (PBMCs) isolated from RA patients. As the positive control, 10 ng/ml of methylprednisolone (MP) showed the antiproliferation effect on mitogen‐activated PBMCs of RA patients significantly (*p < .05). Meanwhile, MP decreased the frequency of CD4+ CD25+ T cells and suppressed the secretion of inflammatory Th1/Th2/Th17 cytokines such as IL‐4, IL‐6, IL‐10, IL‐17, IFN‐γ, and TNF‐α. However, SN at concentrations of 0.3–30 μM, showed little suppressive effects on the proliferation of PBMCs of RA patients. We did not observe any suppressive effects of SN on percentages of CD4+ T cells and CD4+ CD25+ T cells in the mitogen‐activated PBMCs of RA patients. The influence of SN on the percentage of CD4+ CD25+ Foxp3+ T cells was also limited. Finally, even 30 μM of SN did not influence the secretion of Th1/Th2/Th17 cytokine significantly. The present study provided evidence that anti‐RA mechanism of SN seems not to be related with the suppressive effects on peripheral T cells.

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Vitamin K1 and Vitamin K2 immunopharmacological effects on the peripheral lymphocytes of healthy subjects and dialysis patients, as estimated by the lymphocyte immunosuppressant sensitivity test

Abstract: The present data suggest that VK2 has immunosuppressive efficacy. VK2 may enhance the immunosuppressive efficacies of glucocorticoids while preventing osteoporosis caused by glucocorticoids.

Cited by 10 publications

References 20 publications

Cytotoxic effects of vitamins K1, K2, and K3 against human T lymphoblastoid leukemia cells through apoptosis induction and cell cycle arrest

Cytotoxic effects of vitamins K1, K2, and K3 against human T lymphoblastoid leukemia cells through apoptosis induction and cell cycle arrest

Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease

Effects of sinomenine on the proliferation, cytokine production, and regulatory T‐cell frequency in peripheral blood mononuclear cells of rheumatoid arthritis patients

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