Experimental Study on 1,25(OH)2D3 Amelioration of Oral Lichen Planus through Regulating NF-κB Signaling Pathway

Abstract

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)₂D₃ 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-κB (NF-κB) inhibitor and by activator protein 1 (AP-1) inhibitor, VDR-dependent 1,25(OH)₂D₃ blocked the activation of phosphorylated-NF-κB p65 rather than c-Jun/c-Fos in the presence of LPS stimulation.

Conclusion

These results suggest that 1,25(OH)₂D₃ plays an anti-inflammatory role in OLP by mediating NF-κB 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.

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