Department of Dermatology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, P.R. China.
China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8863-8867. doi: 10.3892/mmr.2017.7689. Epub 2017 Oct 2.
Atopic dermatitis (AD) is characterized by a defective skin barrier, which increases the penetration of allergens and pathogens through the skin. The role of interleukin (IL)‑17, a pro‑inflammatory cytokine, in the pathogenesis of AD remains to be elucidated. The present study aimed to examine the effects of IL‑17 on skin barrier proteins in the HaCaT cell line. The expression levels of filaggrin (FLG) and involucrin (IVL) were evaluated by reverse transcription‑quantitative polymerase chain reaction and western blot analyses of the HaCaT cells following IL‑17 simulation. The role of IL‑17 was further examined by using small molecule inhibitors of extracellular signal‑regulated kinase (ERK) and P38. Treatment of the HaCaT cells with IL‑17 resulted in reduced expression levels of FLG and IVL at the mRNA and protein levels. In addition, the gene expression levels of FLG and IVL were significantly reduced in the HaCaT cells by IL‑4. Treatment with the mitogen‑activated protein kinase (MAPK) inhibitors, SB203580 and PD98059, significantly inhibited the effects of IL‑17 on the gene and protein expression levels of FLG and IVL. Finally, the protein levels of phosphorylated ERK and P38 were significantly increased following IL‑17 stimulation. Taken together, the results revealed that IL‑17 reduced the expression of FLG and IVL in HaCaT cells, and this effect involved the P38/ERK MAPK signaling pathways.
特应性皮炎（AD）的特征是皮肤屏障缺陷，这会增加过敏原和病原体通过皮肤的渗透。白细胞介素（IL）-17 作为一种促炎细胞因子，其在 AD 发病机制中的作用仍有待阐明。本研究旨在研究 IL-17 对 HaCaT 细胞系中皮肤屏障蛋白的影响。通过反转录-定量聚合酶链反应和 Western blot 分析，检测 IL-17 刺激后 HaCaT 细胞中丝聚合蛋白（FLG）和内披蛋白（IVL）的表达水平。通过使用细胞外信号调节激酶（ERK）和 P38 的小分子抑制剂进一步研究了 IL-17 的作用。IL-17 处理 HaCaT 细胞导致 FLG 和 IVL 的 mRNA 和蛋白水平表达降低。此外，IL-4 显著降低了 HaCaT 细胞中 FLG 和 IVL 的基因表达水平。丝裂原活化蛋白激酶（MAPK）抑制剂 SB203580 和 PD98059 的处理显著抑制了 IL-17 对 FLG 和 IVL 基因和蛋白表达水平的影响。最后，IL-17 刺激后 ERK 和 P38 的磷酸化蛋白水平显著增加。综上所述，结果表明 IL-17 降低了 HaCaT 细胞中 FLG 和 IVL 的表达，这一作用涉及 P38/ERK MAPK 信号通路。
