Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.
Experimental Research Center, China Academy of Chinese Medical Sciences.
Biol Pharm Bull. 2021;44(1):7-17. 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.
维生素 K2 被认为对小儿特应性皮炎患者的外周血单个核细胞（PBMC）具有抑制作用。我们从丝裂原激活的蛋白激酶信号分子的角度研究了维生素 K2 对特应性皮炎患者 T 细胞丝裂原激活的 PBMC 增殖和细胞因子产生的分子靶标。研究人群包括 16 名儿科维生素 K2 患者和 21 名健康受试者。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）和细胞计数测定评估维生素 K2 对刀豆蛋白 A 激活的 PBMC 增殖的影响。通过细胞因子珠阵列测定分析血浆和 PBMC 培养上清液中的辅助性 T（Th）1/Th2/Th17 细胞因子谱。通过酶联免疫吸附测定（ELISA）测定检查刀豆蛋白 A 激活的 PBMC 中的丝裂原激活蛋白激酶信号分子。在 10-100μM 时，维生素 K2 显著抑制特应性皮炎患者和健康受试者来源的丝裂原激活 PBMC 的增殖（p<0.05）。特应性皮炎患者血浆和 PBMC 培养上清液中的白细胞介素（IL）-10 浓度明显高于健康受试者（p<0.05）。特应性皮炎 PBMC 培养上清液中的 IL-2 浓度明显低于健康 PBMC（p<0.05）。维生素 K2 显著抑制 IL-17A、IL-10 和肿瘤坏死因子 α（TNF-α）的产生（p<0.05），并增加特应性皮炎 PBMC 培养上清液中的 IL-2 产生（p<0.01）。在 10-100μM 时，维生素 K2 显著降低特应性皮炎 PBMC 中 Mek1、细胞外信号调节激酶（ERK）1/2 丝裂原激活蛋白激酶和应激激活蛋白激酶/c-Jun N 末端激酶（JNK）的表达（p<0.05）。维生素 K2 可能通过抑制丝裂原激活的蛋白激酶-Mek1-ERK1/2 和 SAPK/JNK 信号通路来减轻特应性皮炎患者激活的 T 细胞免疫。
