Department of Dermatology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Toyama, Japan.
Department of Pathology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Toyama, Japan.
Exp Dermatol. 2023 Dec;32(12):2160-2165. doi: 10.1111/exd.14797. Epub 2023 Mar 30.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with elevated interleukin (IL)-4 and IL-13 signatures and extensive barrier dysfunction, which is correlated with the downregulation of filaggrin (FLG). FLG is a member of the S100 fused-type protein family and this family also includes cornulin (CRNN), filaggrin-2 (FLG2), hornerin (HRNR) repetin (RPTN), trichohyalin (TCHH) and trichohyalin-like 1 (TCHHL1). The present study aimed to examine the effects of IL-4 and IL-13 and the downregulation of FLG on the expression of S100 fused-type proteins using a three-dimensional (3D) AD skin model by immunohistochemical study and quantitative polymerase chain reaction. In the 3D AD skin model, which was generated by a stimulation of recombinant IL-4 and IL-13, the expression of FLG, FLG2, HRNR and TCHH was decreased, while that of RPTN was increased in comparison to the 3D control skin. In the FLG knockdown (KD) 3D skin model, which was generated using FLG siRNA, the expression of HRNR was increased. The expression of the other proteins did not differ to a statistically significant extent. The expression of fused-S100 type protein family members may differ in AD skin. This suggests that these proteins play different roles in the pathogenesis of AD.
特应性皮炎(AD)是一种慢性炎症性皮肤疾病,具有较高的白细胞介素(IL)-4 和 IL-13 特征和广泛的屏障功能障碍,这与丝聚合蛋白(FLG)的下调有关。FLG 是 S100 融合蛋白家族的成员,该家族还包括兜甲蛋白(CRNN)、FLG2、角蛋白丝聚合蛋白(HRNR)、重复蛋白(RPTN)、毛角蛋白(TCHH)和毛角蛋白样蛋白 1(TCHHL1)。本研究旨在通过免疫组织化学研究和定量聚合酶链反应,检查白细胞介素 4 和白细胞介素 13 的作用以及 FLG 的下调对三维(3D)AD 皮肤模型中 S100 融合蛋白表达的影响。在重组白细胞介素 4 和白细胞介素 13 刺激下产生的 3D AD 皮肤模型中,与 3D 对照皮肤相比,FLG、FLG2、HRNR 和 TCHH 的表达减少,而 RPTN 的表达增加。在使用 FLG siRNA 生成的 FLG 敲低(KD)3D 皮肤模型中,HRNR 的表达增加。其他蛋白质的表达没有统计学上的显著差异。融合 S100 型蛋白家族成员的表达在 AD 皮肤中可能不同。这表明这些蛋白在 AD 的发病机制中发挥不同的作用。