‘Psoriasis 1’ reduces psoriasis‑like skin inflammation by inhibiting the VDR‑mediated nuclear NF‑κB and STAT signaling pathways

2018 
‘Psoriasis 1’, a Chinese herbal medicine (CHM) formulation, is extensively used to treat psoriasis in China. Although this CHM formulation yields good therapeutic effect, the underlying mechanism of how this works remains unknown. The present study aimed to test the hypothesis that the CHM formulation ‘psoriasis 1’ inhibits vitamin D receptor (VDR)-mediated inflammation in psoriasis. To test this, a model of psoriasis was established by stimulating keratinocytes (HaCaT cells) with tumor necrosis factor (TNF)-α; these cells were subsequently transfected with a lentiviral VDR RNA interference expression vector. The expression levels of 25-hydroxyvitamin D3 (25HVD3), TNF-α, interleukin (IL)-4, IL-1, IL-17C, IL-23 and IL-6 were measured using ELISA, and the expression levels of VDR, inhibitor of nuclear factor (NF)-κB (IKK), NF-κB, signal transducer and activator of transcription (STAT) 3 and STAT4 were measured using reverse transcription-quantitative polymerase chain reaction analysis and western blotting. It was observed that ‘psoriasis 1’ downregulated the concentrations of TNF-α, IFN-γ, IL-22, IL-17C, IL-1β and IL-4, and upregulated the concentration of 25HVD3; furthermore, ‘psoriasis 1’ downregulated the expression levels of NF-κB, phosphorylated (p)-NF-κB, IKK, p-IKK, STAT3, p-STAT3, STAT4 and p-STAT4, and upregulated the expression level of VDR in TNF-α-induced HaCaT cells. These results suggested that ‘psoriasis 1’ suppressed the inflammatory response and the activation of the NF-κB and STAT signaling pathways. In addition, it was identified that silencing VDR expression decreased the levels of TNF-α, IFN-γ, IL-22, IL-17C, IL-1β and IL-4, and increased the level of 25HVD3; silencing VDR expression additionally downregulated the expression levels of NF-кB, p-NF-кB, IKK, p-IKK, STAT3, p-STAT3, STAT4 and p-STAT4, and upregulated the level of VDR in TNF-α-induced HaCaT cells. It was concluded that ‘psoriasis 1’ exerts inflammation-suppressive effects in psoriasis by suppressing the NF-кB and STAT signaling pathways.
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