Department of Dermatology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
Mol Med Rep. 2020 Oct;22(4):2715-2722. doi: 10.3892/mmr.2020.11348. Epub 2020 Jul 20.
Psoriasis is one of the most common chronic inflammatory skin diseases, it is characterized by hyperproliferation of keratinocytes and infiltration of inflammatory cells. Several in vitro studies have reported that interleukin (IL)‑22 is involved in excessive proliferation and abnormal differentiation of human keratinocytes. However, the association between IL‑22 and CCAAT enhancer binding protein α (C/EBPα) in the pathogenesis of psoriasis remains unclear. Therefore, the present study aimed to investigate the association between IL‑22 and C/EBPα, and the effects of IL‑22 on the proliferation and differentiation of keratinocytes. Keratinocytes were treated with different concentrations of IL‑22 (30, 60 and 90 ng/ml) and subsequently cells were collected at different time intervals. The expression levels of the key molecules of the mitogen‑activated protein kinase (MAPK) signaling pathway were detected using western blot analysis. In addition, the effect of IL‑22 on the proliferation rate of keratinocytes and the mRNA expression levels of C/EBPα were determined using a Cell Counting Kit‑8 assay and reverse transcription‑quantitative PCR, respectively. Furthermore, keratinocytes were transfected with C/EBPα small interfering (si)RNA or control using Lipofectamine® 2000. The results revealed that IL‑22 significantly induced the proliferation of keratinocytes and the expression of phosphorylated (p)‑JNK, p‑ERK and p‑p38 (P<0.05). Additionally, IL‑22 significantly inhibited the differentiation of keratinocytes, and the mRNA and protein expression of C/EBPα (P<0.05). Furthermore, downregulation of C/EBPα increased the proliferation rate of keratinocytes and reduced the expression levels of cytokeratin 10 and involucrin. Therefore, these results suggested that the effect of IL‑22 on the proliferation and differentiation of keratinocytes may be mediated via the regulation of the MAPK signaling pathway and the expression of C/EBPα.
银屑病是最常见的慢性炎症性皮肤病之一,其特征为角质形成细胞过度增殖和炎症细胞浸润。几项体外研究报道,白细胞介素(IL)-22 参与了人角质形成细胞的过度增殖和异常分化。然而,IL-22 与银屑病发病机制中的 CCAAT 增强子结合蛋白α(C/EBPα)之间的关联尚不清楚。因此,本研究旨在探讨 IL-22 与 C/EBPα 之间的关联,以及 IL-22 对角质形成细胞增殖和分化的影响。用不同浓度的 IL-22(30、60 和 90ng/ml)处理角质形成细胞,随后在不同时间点收集细胞。采用蛋白质印迹法检测丝裂原激活蛋白激酶(MAPK)信号通路关键分子的表达水平。此外,采用细胞计数试剂盒-8 法检测 IL-22 对角质形成细胞增殖率的影响,采用逆转录-定量 PCR 检测 C/EBPα 的 mRNA 表达水平。进一步用 Lipofectamine®2000 将 C/EBPα 小干扰(si)RNA 或对照转染入角质形成细胞。结果显示,IL-22 显著诱导角质形成细胞增殖和磷酸化(p)-JNK、p-ERK 和 p-p38 的表达(P<0.05)。此外,IL-22 显著抑制角质形成细胞分化,C/EBPα 的 mRNA 和蛋白表达降低(P<0.05)。此外,下调 C/EBPα 可增加角质形成细胞的增殖率,并降低角蛋白 10 和内披蛋白的表达水平。因此,这些结果表明,IL-22 对角质形成细胞增殖和分化的影响可能是通过调节 MAPK 信号通路和 C/EBPα 的表达来介导的。