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Published Online: 14 July 2016

Inhibition of TNF-α, IL-1α, and IL-1β by Pretreatment of Human Monocyte-Derived Macrophages with Menaquinone-7 and Cell Activation with TLR Agonists In Vitro

Publication: Journal of Medicinal Food
Volume 19, Issue Number 7


Circulatory markers of low-grade inflammation such as tumor necrosis factor-alpha (TNF-α), interleukin-1 alpha (IL-1α), and interleukin-1 beta (IL-1β) positively correlate with endothelial damage, atheroma formation, cardiovascular disease, and aging. The natural vitamin K2-menaquinone-7 (MK-7) added to the cell culture of human monocyte-derived macrophages (hMDMs) at the same time as toll-like receptor (TLR) agonists did not influence the production of TNF-α. When the cells were pretreated up to 6 h with MK-7 before treatment with TLR agonists, MK-7 did not inhibit significantly the production of TNF-α after the TLR activation. However, 30 h pretreatment of hMDMs with at least 10 μM of MK-7 effectively and dose dependently inhibited the proinflammatory function of hMDMs. Pretreatment of hMDMs with 10 μM of MK-7 for 30 h resulted in 20% inhibition of TNF-α production after lipopolysaccharide (LPS) activation (P < .05) and 43% inhibition after macrophage-activating lipopeptide (MALP) activation (P < .001). Pathogen-associated molecular pattern (PMPP) activation was inhibited by 20% with MK-7 pretreatment; however, this inhibition was not statistically significant. The 30 h pretreatment of a THP-1-differentiated monocyte cell line with MK-7 resulted in a dose-dependent downregulation of TNFα, IL-1α, and IL-1β gene expression as evaluated by RNA semiquantitative reverse transcription polymerase chain reaction (RT-PCR). MK-7 is able to modulate immune and inflammatory reactions in the dose–response inhibition of TNF-α, IL-1α, and IL-1β gene expression and protein production by the healthy hMDMs in vitro.

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Published In

cover image Journal of Medicinal Food
Journal of Medicinal Food
Volume 19Issue Number 7July 2016
Pages: 663 - 669
PubMed: 27200471


Published online: 14 July 2016
Published in print: July 2016
Published ahead of print: 20 May 2016
Accepted: 11 April 2016
Received: 25 February 2016


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Min-Hsiung Pan
Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, College of Life Science, Huanggang Normal University, Hubei, China.
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
Institute of Food Sciences and Technology, National Taiwan University, Taipei, Taiwan.
Katarzyna Maresz
The International Science and Health Foundation, Krakow, Poland.
Pei-Sheng Lee
Institute of Food Sciences and Technology, National Taiwan University, Taipei, Taiwan.
Jia-Ching Wu
Institute of Food Sciences and Technology, National Taiwan University, Taipei, Taiwan.
Chi-Tang Ho
Department of Food Science, Rutgers University, New Brunswick, New Jersey, USA.
Janusz Popko
Medical Institute of the State College of Computer Science and Business Administration, Łomża, Poland.
Department of Pediatric Orthopedics, Medical University of Białystok, Białystok, Poland.
Dilip S. Mehta
Viridis BioPharma Private Limited, Mumbai, India.
Sidney J. Stohs
Creighton University Medical Center, Omaha, Nebraska, USA.
Vladimir Badmaev
American Medical Holdings Incorporated, New York, New York, USA.
NattoPharma ASA, Oslo, Norway.


Address correspondence to: Vladimir Badmaev, MD, PhD, American Medical Holdings Incorporated, 1440 Forest Hill Road, New York, NY 10314, USA, E-mail: [email protected]

Author Disclosure Statement

No competing financial interests exist.

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