Department of Dermatology, Tianjin TEDA Hospital, Tianjin, P.R. China.
Department of Internal Medicine, Tianjin Beichen Traditional Chinese Medicine Hospital, Tianjin, P.R. China.
Bioengineered. 2022 Jan;13(1):1530-1540. doi: 10.1080/21655979.2021.2021701.
Psoriasis is a common chronic immune-mediated disease that often has a serious negative impact on the physical and mental health of patients. Dihydroartemisinin (DHA) is a drug with anti-fibrotic and anti-inflammatory effects that may be involved in the autoimmune regulation of immune diseases. However, the effects of DHA on psoriasis have not been reported comprehensively. Therefore, the aim of this study was to investigate the effect of DHA on abnormal proliferation and inflammation of epidermal keratinocyte cells in psoriasis and its mechanism of action. IL-17A-induced human epidermal keratin-forming cells (HaCaT) were used as a model. And after induction exposure to different concentrations of DHA, CCK-8, EDU staining, wound healing and Western blotting were performed to assess cell viability, proliferation, migration, differentiation and inflammatory factors, respectively. Subsequently, agonists of fibroblast growth factor receptor 1 (FGFR1) were added and the above experiments were repeated. The results showed that DHA obviously inhibited IL-17A-induced hyperproliferation, migration and expression of inflammatory factors in HaCaT cells. Furthermore, FGFR1 was highly expressed in IL-17A-induced HaCaT cells, and DHA inhibited its expression. However, the inhibitory effect of DHA on IL-17A-induced HaCaT cells was reversed after the addition of FGFR1 agonist. In conclusion, DHA could inhibit IL-17A-induced hyperproliferation and inflammation of keratinocytes by targeting FGFR1, which also provided a new target for the treatment of psoriasis.
银屑病是一种常见的慢性免疫介导性疾病，常给患者的身心健康带来严重负面影响。二氢青蒿素（DHA）是一种具有抗纤维化和抗炎作用的药物，可能参与免疫性疾病的自身免疫调节。然而，DHA 对银屑病的影响尚未得到全面报道。因此，本研究旨在探讨 DHA 对银屑病表皮角质形成细胞异常增殖和炎症的影响及其作用机制。采用白细胞介素 17A（IL-17A）诱导的人表皮角质形成细胞（HaCaT）作为模型。诱导暴露于不同浓度的 DHA 后，通过 CCK-8、EDU 染色、划痕愈合和 Western blot 分别评估细胞活力、增殖、迁移、分化和炎症因子。随后，加入成纤维细胞生长因子受体 1（FGFR1）激动剂，并重复上述实验。结果表明，DHA 明显抑制了 IL-17A 诱导的 HaCaT 细胞过度增殖、迁移和炎症因子的表达。此外，IL-17A 诱导的 HaCaT 细胞中 FGFR1 高表达，而 DHA 抑制其表达。然而，加入 FGFR1 激动剂后，DHA 对 IL-17A 诱导的 HaCaT 细胞的抑制作用被逆转。综上所述，DHA 通过靶向 FGFR1 抑制 IL-17A 诱导的角质形成细胞过度增殖和炎症，为银屑病的治疗提供了新的靶点。
