Exogenous Vitamins K Exert Anti-Inflammatory Effects Dissociated from Their Role as Substrates for Synthesis of Endogenous MK-4 in Murine Macrophages Cell Line

• Published in: Cells (Basel, Switzerland) Switzerland), 2021-06, Vol.10 (7), p.1571
• Main Authors: Kieronska-Rudek, Anna, Kij, Agnieszka, Kaczara, Patrycja, Tworzydlo, Anna, Napiorkowski, Marek, Sidoryk, Katarzyna, Chlopicki, Stefan
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Anticoagulants; Atorvastatin; Atorvastatin - pharmacology; Calcification; Cell culture; Cell Respiration - drug effects; Cyclooxygenase 2 - biosynthesis; Cyclooxygenase-2; Cytokines; Cytokines - biosynthesis; Eicosanoids - biosynthesis; endogenous MK-4; Enzyme Induction - drug effects; Enzymes; Gene expression; Inflammation; Lipopolysaccharides - pharmacology; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Mice; Mitochondria - drug effects; Mitochondria - metabolism; Nitrates; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type II - metabolism; Proteins; RAW 264.7 Cells; statin; Substrate Specificity - drug effects; Vitamin K - pharmacology; Vitamins; vitamins K
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10071571

Vitamins K exert a range of activities that extend far beyond coagulation and include anti-inflammatory effects, but the mechanisms involved in anti-inflammatory action remain unclear. In the present study, we showed that various forms of exogenous vitamins-K , K , K (MK-4, MK-5, MK-6 and MK-7)-regulated a wide scope of inflammatory pathways in murine macrophages in vitro, including NOS-2, COX-2, cytokines and MMPs. Moreover, we demonstrated for the first time that macrophages are able to synthesise endogenous MK-4 on their own. Vitamins with shorter isoprenoid chains-K , K and MK-5-exhibited stronger anti-inflammatory potential than vitamins with longer isoprenoid chains (MK-6 and MK-7) and simultaneously were preferably used as a substrate for MK-4 endogenous production. Most interesting, atorvastatin pretreatment inhibited endogenous MK-4 production but had no impact on the anti-inflammatory activity of vitamins K. In summary, our results demonstrate that macrophages are able to synthesise endogenous MK-4 using exogenous vitamins K, and statin inhibits this process. However, the anti-inflammatory effect of exogenous vitamins K was independent of endogenous MK-4 synthesis.