Inhibition of TNF-a, IL-1a, and IL-1b by Pretreatment of Human Monocyte-Derived Macrophages with Menaquinone-7 and Cell Activation with TLR Agonists In Vitro (Pan MH et al.)
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 Journal of Medicinal Food has published a new study that successfully tested and confirmed the role of vitamin K2 as MK-7 (menaquinone-7) in modulation of the immune and inflammatory biomarkers.
The study, “Inhibition of TNF-a, IL-1a, and IL-1b by Pretreatment of Human Monocyte-Derived Macrophages with Menaquinone-7 and Cell Activation with TLR Agonists In Vitro,” is significant because it confirms another mechanism by which vitamin K2 supports cardiovascular health by impact markers of inflammation.
“Chronic inflammation is considered an underlying pathology of many diseases that remain poorly understood and treated,” the researchers wrote. “Cardiovascular disease (CVD), a leading cause of mortality in the world, is not only considered as a disorder of lipid accumulation, but also as a disease characterized by low-grade inflammation of the endothelial cells and an inappropriate healing response of the vascular lining.”
The commonly recognized function of vitamin K is a cofactor for c-glutamyl carboxylase, an endoplasmic enzyme involved in the posttranslational carboxylation (activation) of proteins with glutamic acid (Glu) residues into c-carboxyglutamate (Gla). With the carboxylation of glutamic acid residues on the protein substrate, a negative chemical group is formed that attracts and binds positively charged calcium cation. Vitamin K2, in particular, is responsible for carboxylation and activation of osteocalcin, which is essential for physiology of bone-building cells, osteoblasts. Vitamin K2 helps in carboxylation and activation of another protein besides osteocalcin, that is, matrix GLA protein (MGP), important for elasticity and prevention of calcification of blood vessels.
To that end, researchers evaluated high-purity natural vitamin K2 (98.4% menaquinone-7, MK-7) in vitro for its potential to inhibit gene expression and production of pro-inflammatory markers by human monocyte-derived macrophages (hMDMs) from two sources (hMDMs and THP-1).
The results showed that the MK-7 form of vitamin K2 is able to dose dependently inhibit TNF-a, IL-1a, and IL-1b gene expression and protein production by healthy hMDMs in vitro. According to the researchers, “In view of these encouraging findings on the anti-inflammatory properties of MK-7, we plan to test additional biomarkers of immune and inflammatory response in this form of vitamin K2 in vitro. This work may elucidate the anti-inflammatory mechanism of vitamin K2 and establish the potential biomarker targets in clinical testing of the role of MK-7 in the cardiovascular health as well as other chronic degenerative conditions.”
Pan MH, Maresz K, Lee PS, Wu JC, Ho CT, Popko J, Mehta DS, Stohs SJ, Badmaev V. Inhibition of TNF-α, IL-1α, and IL-1β by Pretreatment of Human Monocyte-Derived Macrophages withMenaquinone-7 and Cell Activation with TLR Agonists In Vitro. J Med Food. 2016 May 20. [Epub ahead of print]