Department of Dermatology, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, P.R. China.
Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.
Mol Med Rep. 2018 Sep;18(3):2733-2743. doi: 10.3892/mmr.2018.9262. Epub 2018 Jul 9.
'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.
“ psoriasis 1 ”,一种中药( CHM )配方,在中国被广泛用于治疗银屑病。尽管这种 CHM 配方产生了很好的治疗效果,但它的工作机制尚不清楚。本研究旨在验证这样一种假设,即 CHM 配方“ psoriasis 1 ”抑制维生素 D 受体( VDR )介导的银屑病炎症。为了验证这一点,通过用肿瘤坏死因子( TNF ) -α刺激角质形成细胞( HaCaT 细胞)来建立银屑病模型;随后将这些细胞用慢病毒 VDR RNAi 表达载体转染。使用 ELISA 测量 25-羟维生素 D3 ( 25HVD3 )、 TNF-α、白细胞介素( IL ) -4 、 IL-1 、 IL-17C 、 IL-23 和 IL-6 的表达水平,并使用逆转录-定量聚合酶链反应分析和蛋白质印迹法测量 VDR 、核因子( NF ) -κB 抑制剂( IKK ) 、 NF-κB 、信号转导和转录激活因子( STAT ) 3 和 STAT4 的表达水平。结果观察到,“ psoriasis 1 ”下调 TNF-α、 IFN-γ 、 IL-22 、 IL-17C 、 IL-1β和 IL-4 的浓度,上调 25HVD3 的浓度;此外,“ psoriasis 1 ”下调 TNF-α诱导的 HaCaT 细胞中 NF-κB 、磷酸化( p ) -NF-κB 、 IKK 、 p-IKK 、 STAT3 、 p-STAT3 、 STAT4 和 p-STAT4 的表达水平,并上调 VDR 的表达水平。这些结果表明,“ psoriasis 1 ”抑制了炎症反应和 NF-κB 和 STAT 信号通路的激活。此外,鉴定出沉默 VDR 表达降低了 TNF-α、 IFN-γ 、 IL-22 、 IL-17C 、 IL-1β和 IL-4 的水平,并增加了 25HVD3 的水平;沉默 VDR 表达还下调了 TNF-α诱导的 HaCaT 细胞中 NF-κB 、 p-NF-κB 、 IKK 、 p-IKK 、 STAT3 、 p-STAT3 、 STAT4 和 p-STAT4 的表达水平,并上调了 VDR 的水平。结论是,“ psoriasis 1 ”通过抑制 NF-κB 和 STAT 信号通路在银屑病中发挥抗炎作用。