title: 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.
abstract: 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.
authors.affiliation: 1 Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization, College of Life Science, Huanggang Normal University , Hubei, China .|2 Department of Medical Research, China Medical University Hospital, China Medical University , Taichung, Taiwan .|3 Department of Health and Nutrition Biotechnology, Asia University , Taichung, Taiwan .|4 Institute of Food Sciences and Technology, National Taiwan University , Taipei, Taiwan .
authors.forename: Min-Hsiung
authors.initials: MH
authors.lastname: Pan
authors.affiliation: 5 The International Science and Health Foundation , Krakow, Poland .
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Maresz
authors.affiliation: 4 Institute of Food Sciences and Technology, National Taiwan University , Taipei, Taiwan .
authors.forename: Pei-Sheng
authors.initials: PS
authors.lastname: Lee
authors.affiliation: 4 Institute of Food Sciences and Technology, National Taiwan University , Taipei, Taiwan .
authors.forename: Jia-Ching
authors.initials: JC
authors.lastname: Wu
authors.affiliation: 6 Department of Food Science, Rutgers University , New Brunswick, New Jersey, USA.
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.affiliation: 7 Medical Institute of the State College of Computer Science and Business Administration , Łomża, Poland .|8 Department of Pediatric Orthopedics, Medical University of Białystok , Białystok, Poland .
authors.forename: Janusz
authors.initials: J
authors.lastname: Popko
authors.affiliation: 9 Viridis BioPharma Private Limited , Mumbai, India .
authors.forename: Dilip S
authors.initials: DS
authors.lastname: Mehta
authors.affiliation: 10 Creighton University Medical Center , Omaha, Nebraska, USA.
authors.forename: Sidney J
authors.initials: SJ
authors.lastname: Stohs
authors.affiliation: 11 American Medical Holdings Incorporated , New York, New York, USA.|12 NattoPharma ASA , Oslo, Norway .
authors.forename: Vladimir
authors.initials: V
authors.lastname: Badmaev
mesh_terms: D000893:Anti-Inflammatory Agents; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors* / Q000235:genetics; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D051193:Toll-Like Receptors / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; C508584:IL1A protein, human; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D024482:Vitamin K 2; C062629:menaquinone 7
keywords: MenaQ7® Crystals; TNF-α; cardiovascular; inflammation; menaquinone-7