Vitamin K2 Suppresses Proliferation and Inflammatory Cytokine Production in Mitogen-Activated Lymphocytes of Atopic Dermatitis Patients through the Inhibition of Mitogen-Activated Protein Kinases
- 1 January 2021
- journal article
- research article
- Published by Pharmaceutical Society of Japan in Biological & Pharmaceutical Bulletin
- Vol. 44 (1), 7-17
- https://doi.org/10.1248/bpb.b20-00079
Abstract
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.Keywords
This publication has 39 references indexed in Scilit:
- Mitogen-activated protein kinases in innate immunityNature Reviews Immunology, 2013
- Prevalence of Childhood Atopic Dermatitis: An Urban and Rural Community-Based Study in Shanghai, ChinaPLOS ONE, 2012
- Differential Requirement for c-Jun N-terminal Kinase 1 in Lung Inflammation and Host DefensePLOS ONE, 2012
- IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potentialClinical Science, 2012
- Mast Cell Interleukin-2 Production Contributes to Suppression of Chronic Allergic DermatitisImmunity, 2011
- Activation of coagulation in bullous pemphigoid and other eosinophil-related inflammatory skin diseasesClinical and Experimental Immunology, 2011
- Vitamin D Analogs Differentially Control Antimicrobial Peptide/“Alarmin”Expression in PsoriasisPLOS ONE, 2009
- IL-22–producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17–producing TH17 T cellsJournal of Allergy and Clinical Immunology, 2009
- Occupational allergy as a challenge to developing countriesToxicology, 2004
- MAP Kinases in the Immune ResponseAnnual Review of Immunology, 2002