Experimental study on 1,25(OH)2D3 amelioration of oral lichen planus through regulating NF-κB signaling pathway

Experimental study on 1,25(OH)2D3 amelioration of oral lichen planus through regulating NF-κB signaling pathway
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DOI:
10.1111/odi.12659
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发表时间:
2017-09-01
期刊:
影响因子:
3.8
通讯作者:
Zhang, F.
Zhang, F.
中科院分区:
医学3区
文献类型:
--
作者:
Du, J.;Li, R.;Zhang, F.

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目的:探讨维生素D(VD)/维生素D受体(VDR)在口腔扁平苔藓(OLP)发病过程中的保护作用及其机制。方法:采用H&E染色、髓过氧化物酶(MPO)法、定量聚合酶链式反应(QPCR)、Western blotting和ELISA法对口腔扁平苔藓(OLP)组织和血清进行检测。对脂多糖诱导的角质形成细胞进行定量聚合酶链式反应、Western blotting、ELISA法和siRNA转染法,观察维生素D和VDR的功能。结果:口腔扁平苔藓患者病变组织中VDR的缺失与激活的辅助性T细胞1型(Th1)驱动的炎症反应有关。重要的是,口腔扁平苔藓患者的血清25-羟基维生素D水平持续下降。在培养的细胞模型中,1,25(OH)(2)D-3可抑制脂多糖(LPS)诱导的角质形成细胞HaCat细胞过度产生促炎因子。结论:1,25(OH)(2)D-3在口腔扁平苔藓中的抗炎作用是通过VDR依赖的1,25(OH)(2)D-3而不是c-Jun/c-Fos来实现的。结论:1,25(OH)(2)D-3在口腔扁平苔藓中具有抗炎作用预测维生素D补充量可能是口腔扁平苔藓治疗的一种潜在策略。
OBJECTIVE: To explore the protective function of vitamin D (VD)/vitamin D receptor (VDR) on the development of oral lichen planus (OLP) and elaborate the underling mechanism of it.METHODS: H&E staining, myeloid peroxidase (MPO) assays, quantitative PCR (qPCR), Western blotting, and Elisa were used to test the human biopsies and serum. QPCR, Western blotting, Elisa, and siRNA transfection were also performed in LPS-induced keratinocytes to observe the functions of vitamin D and VDR.RESULTS: The lack of VDR in the diseased biopsies from OLP patients was associated with activated helper T-cell type 1 (Th1)-driven inflammatory response. Importantly, the status of serum 25-hydroxyvitamin D of OLP patients was reduced consistently. In a cultured cell model, 1,25(OH)(2)D-3 could downregulate excessive production of pro-inflammatory factors induced by lipopolysaccharide (LPS) in keratinocyte HaCat cells. Mechanistically, even though LPS-induced cytokines in keratinocytes were inhibited both by nuclear factor-kappa B (NF-kappa B) inhibitor and by activator protein 1 (AP-1) inhibitor, VDR-dependent 1,25(OH)(2)D-3 blocked the activation of phosphorylated-NF-kappa B p65 rather than c-Jun/c-Fos in the presence of LPS stimulation.CONCLUSION: These results suggest that 1,25(OH)(2)D-3 plays an anti-inflammatory role in OLP by mediating NF-kappa B signaling pathway but not AP-1 signaling pathway with a VDR-dependent manner, predicting vitamin D supplement may be a potential strategy for the OLP management.