Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710004, China.
Br J Dermatol. 2016 Aug;175(2):314-24. doi: 10.1111/bjd.14481. Epub 2016 May 14.
Calcipotriol ameliorates psoriasis through inducing keratinocyte apoptosis and inhibiting nuclear factor kappa B (NF-κB) activation, while zinc finger protein A20 exhibits an anti-apoptotic effect on various types of cells.
To understand the potential role of A20 in calcipotriol function.
The A20 levels were evaluated in the psoriatic skins from both human patients and K14-vascular endothelial growth factor (VEGF) transgenic mice that received or did not receive topical calcipotriol treatment. The in vitro effect of calcipotriol on A20 expression and the downstream NF-κB pathway was studied using a model of human foreskin keratinocytes (HFKs) that were stimulated with psoriatic cytokines [M5, a cocktail of interleukin (IL)-1a, IL-17A, IL-22, Oncostatin M and tumour necrosis factor-α, each at 10 ng mL(-1) ].
A20 expression was enhanced in both psoriatic tissues and keratinocytes when compared with controls, but decreased on calcipotriol treatment. The transfection of A20 small interfering RNA (siRNA) improved cell differentiation, and inhibited psoriatic inflammation in a HFK model. Moreover, the nuclear expression of NF-κB p65 decreased on A20 downregulation in psoriatic tissues and keratinocytes. Interestingly, calcipotriol enhanced the binding of A20 to ring finger protein 114 (RNF114) and A20-binding inhibitor of NF-κB-1 (ABIN-1) in HFKs, two negative regulators of the NF-κB pathway.
Calcipotriol exhibits its antipsoriatic function through suppressing A20 expression and stabilizing negative regulators of the NF-κB pathway.
卡泊三醇通过诱导角质形成细胞凋亡和抑制核因子 κB（NF-κB）激活来改善银屑病，而锌指蛋白 A20 对各种类型的细胞具有抗凋亡作用。
了解 A20 在卡泊三醇功能中的潜在作用。
评估了接受或未接受局部卡泊三醇治疗的人类患者和 K14-血管内皮生长因子（VEGF）转基因小鼠的银屑病皮肤中的 A20 水平。使用银屑病细胞因子 [M5（白细胞介素（IL）-1a、IL-17A、IL-22、Oncostatin M 和肿瘤坏死因子-α，每种 10ngmL(-1)）的混合物] 刺激的人包皮成纤维细胞（HFK）模型研究了卡泊三醇对 A20 表达和下游 NF-κB 通路的体外影响。
与对照相比，银屑病组织和角质形成细胞中 A20 的表达增强，但在卡泊三醇治疗后减少。A20 小干扰 RNA（siRNA）的转染改善了 HFK 模型中的细胞分化，并抑制了银屑病炎症。此外，在银屑病组织和角质形成细胞中下调 A20 后，NF-κB p65 的核表达减少。有趣的是，卡泊三醇增强了 HFK 中 NF-κB 通路的负调节剂 A20 与环指蛋白 114（RNF114）和 A20 结合抑制物 NF-κB-1（ABIN-1）的结合。
卡泊三醇通过抑制 A20 表达和稳定 NF-κB 通路的负调节剂来发挥其抗银屑病作用。
