Vitamin K2 Suppresses Proliferation and Inflammatory Cytokine Production in Mitogen-Activated Lymphocytes of Atopic Dermatitis Patients through the Inhibition of Mitogen-Activated Protein Kinases

• Published in: Biological & pharmaceutical bulletin Vol. 44; no. 1; pp. 7 - 17
• Main Authors: Suzuki, Shunsuke, Miura, Taro, Zhang, Meiyu, Chiyotanda, Masako, Sugiyama, Kentaro, Kawashima, Hisashi, Tanaka, Sachiko, Hirano, Toshihiko
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.01.2021; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Atopic dermatitis; c-Jun protein; Cell culture; Concanavalin A; cytokine; Cytokines; Dermatitis; Eczema; Enzyme-linked immunosorbent assay; Extracellular signal-regulated kinase; Helper cells; Inflammation; Interleukin 10; Interleukin 2; JNK protein; Kinases; Leukocytes (mononuclear); Lymphocytes T; MAP kinase; Menaquinones; mitogen-activated protein kinase signaling pathway; Pediatrics; Peripheral blood mononuclear cells; Population studies; Protein arrays; Protein kinase; Proteins; Transcription factors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; vitamin K2; cytokine; atopic dermatitis; mitogen-activated protein kinase signaling pathway; vitamin K2
• ISSN: 0918-6158; 1347-5215; 1347-5215
• DOI: 10.1248/bpb.b20-00079

Vitamin K2 is suggested to have a suppressive effect on the peripheral blood mononuclear cells (PBMCs) of pediatric atopic dermatitis patients. We examined the molecular targets of vitamin K2 to suppress proliferation and cytokine production in T-cell mitogen-activated PBMCs of atopic dermatitis patients from the viewpoint of mitogen-activated protein kinase signaling molecules. The study population included 16 pediatric vitamin K2 patients and 21 healthy subjects. The effect of vitamin K2 on concanavalin A-activated PBMC proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell counting assays. T-helper (Th)1/Th2/Th17 cytokine profiles in plasma and PBMC-culture supernatants were analyzed by a cytometric beads array assay. Mitogen-activated protein kinase signaling molecules in concanavalin A-activated PBMCs were examined by enzyme-linked immunosorbent assay (ELISA) assays. At 10–100 µM, vitamin K2 significantly suppressed the proliferation of mitogen-activated PBMCs derived from atopic dermatitis patients and healthy subjects (p < 0.05). The interleukin (IL)-10 concentrations in plasma and the PBMC culture supernatants of atopic dermatitis patients were significantly higher than those of healthy subjects (p < 0.05). The IL-2 concentrations in the culture supernatants of atopic dermatitis PBMCs were significantly lower than those of healthy PBMCs (p < 0.05). Vitamin K2 significantly inhibited the IL-17A, IL-10, and tumor necrosis factor α (TNF-α) production (p < 0.05), and increased the IL-2 production (p < 0.01) in the culture supernatant of atopic dermatitis PBMCs. At 10–100 µM, vitamin K2 markedly decreased the of Mek1, extracellular signal-regulated kinases (ERK)1/2 mitogen-activated protein kinase, and SAPK/c-Jun N-terminal kinase (JNK) expression in atopic dermatitis PBMCs (p < 0.05). Vitamin K2 is suggested to attenuate activated T-cell immunity in atopic dermatitis patients through the inhibition of mitogen-activated protein kinase-Mek1-ERK1/2 and SAPK/JNK signaling pathways.