title: Effects of vitamin K3 and K5 on proliferation, cytokine production, and regulatory T cell-frequency in human peripheral-blood mononuclear cells.
abstract: OBJECTIVE
  The effects of vitamin K (VK) derivatives VK3 and VK5 on human immune cells have not been extensively investigated. We examined the effects of VK3 and VK5 on proliferation, apoptosis, cytokine production, and CD4+CD25+Foxp3+ regulatory T (Treg) cell-frequency in human peripheral blood mononuclear cells (PBMCs) activated by T cell mitogen in vitro.
  
  
  METHODS
  Anti-proliferative effects of VK3 and VK5 on T-cell mitogen activated PBMCs were assessed by WST assay procedures. Apoptotic cells were determined as Annexin V positive/propidium iodide (PI) negative cells. Cytokine concentrations in the supernatant of the culture medium were measured with bead-array procedures followed by analysis with flow cytometry. The CD4+CD25+Foxp3+Treg cells in mitogen-activated PBMCs were stained with fluorescence-labeled specific antibodies followed by flow cytometry.
  
  
  RESULTS
  VK3 and VK5 suppressed the mitogen-activated proliferation of PBMCs significantly at 10-100μM (p<0.05). The data also suggest that VK3 and VK5 promote apoptosis in the mitogen-activated T cells. VK3 and VK5 significantly inhibited the production of tumor necrosis factor (TNF) α, interleukin (IL)-4, -6, and -10 from the activated PBMCs at 10-100μM (p<0.05). In contrast, VK3 and VK5 significantly increased Treg cell-frequency in the activated PBMCs at concentrations more than 10μM (p<0.001).
  
  
  CONCLUSIONS
  Our data suggest that VK3 and VK5 attenuate T cell mediated immunity by inhibiting the proliferative response and inducing apoptosis in activated T cells.
authors: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy Life Sciences, Japan.
authors: Hiroshige
authors: H
authors: Hatanaka
authors: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy Life Sciences, Japan.
authors: Hitomi
authors: H
authors: Ishizawa
authors: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy Life Sciences, Japan.
authors: Yurie
authors: Y
authors: Nakamura
authors: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy Life Sciences, Japan.
authors: Hiroko
authors: H
authors: Tadokoro
authors: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy Life Sciences, Japan.
authors: Sachiko
authors: S
authors: Tanaka
authors: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy Life Sciences, Japan.
authors: Kenji
authors: K
authors: Onda
authors: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy Life Sciences, Japan.
authors: Kentaro
authors: K
authors: Sugiyama
authors: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy Life Sciences, Japan. Electronic address: hiranot@toyaku.ac.jp.
authors: Toshihiko
authors: T
authors: Hirano
mesh_terms: D000328:Adult; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects*; D008297:Male; D012015:Reference Standards; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects*; D024483:Vitamin K 3 / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D024483:Vitamin K 3; C024534:vitamin k5
keywords: CD4+CD25+Foxp3+ regulatory T cells; Cytokines; Peripheral blood mononuclear cells; T cell mitogen; Vitamin K(3); Vitamin K(5)