Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, China.
Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan City Central Hospital, Taiyuan, China.
J Cosmet Dermatol. 2024 Jan;23(1):326-338. doi: 10.1111/jocd.15975. Epub 2023 Aug 27.
Increased angiogenesis is a pathological feature of psoriasis, but the pathomechanisms of angiogenesis in psoriasis are not clear. Interleukin-17A (IL-17A) is the major effect factor in the pathogenesis of psoriasis. Our results showed that IL-17A can promote angiogenesis and cause endothelial cell inflammation. Autophagy plays an important role not only in regulating inflammation, but also in regulating angiogenesis. Whether angiogenesis in psoriasis is related to autophagy remains unclear. In this study, we treated human umbilical vein endothelial cells (HUVECs) with IL-17A to simulate increased angiogenesis to study whether increased angiogenesis in psoriasis is related to autophagy.
Our results showed that treatment of HUVECs with IL-17A significantly increased angiogenesis and expression levels of mRNA for multiple proinflammatory cytokines (CCL20, IL-8, CCL2, IL-6, and IL-1β) and, while decreasing intracellular levels of nitric oxide (NO) and NO synthase (NOS) activity. Moreover, IL-17A inhibited autophagy as shown that IL-17A significantly increased expression levels of LC3II and p62 proteins. Induction of autophagy ameliorated IL-17A-mediated inflammatory response and inhibited angiogenesis, accompanied by increased p-AMPKα(Thr172) and p-ULK1(Ser555) expression, and decreased p-mTOR(Ser2448) and p-ULK1(Ser757) expression. Furthermore, inhibition of either AMPK or lysosomal acidification completely overrode autophagy-induced changes in angiogenesis and NOS activity. Finally, induction of autophagy decreased apoptosis and caspase-3 activity in IL-17A-treated HUVECs.
These results showed that IL-17A is involved in angiogenesis and inflammatory response by inhibiting autophagy through AMPK signaling pathway, suggesting that autophagy may be a new therapeutic target for psoriasis.
血管新生增加是银屑病的一种病理特征，但银屑病血管新生的发病机制尚不清楚。白细胞介素-17A（IL-17A）是银屑病发病机制中的主要作用因子。我们的结果表明，IL-17A 可以促进血管生成并引起内皮细胞炎症。自噬不仅在调节炎症中起重要作用，而且在调节血管生成中也起重要作用。银屑病中的血管生成是否与自噬有关尚不清楚。在这项研究中，我们用 IL-17A 处理人脐静脉内皮细胞（HUVEC）以模拟血管生成增加，以研究银屑病中血管生成增加是否与自噬有关。
我们的结果表明，IL-17A 处理 HUVEC 可显著增加血管生成和多种促炎细胞因子（CCL20、IL-8、CCL2、IL-6 和 IL-1β）的 mRNA 表达水平，同时降低细胞内一氧化氮（NO）水平和一氧化氮合酶（NOS）活性。此外，IL-17A 抑制自噬，表现为 IL-17A 显著增加 LC3II 和 p62 蛋白的表达。自噬的诱导改善了 IL-17A 介导的炎症反应并抑制了血管生成，同时增加了 p-AMPKα（Thr172）和 p-ULK1（Ser555）的表达，降低了 p-mTOR（Ser2448）和 p-ULK1（Ser757）的表达。此外，AMPK 或溶酶体酸化的抑制完全消除了自噬诱导的血管生成和 NOS 活性的变化。最后，自噬的诱导降低了 IL-17A 处理的 HUVEC 中的细胞凋亡和 caspase-3 活性。
这些结果表明，IL-17A 通过 AMPK 信号通路抑制自噬参与血管生成和炎症反应，提示自噬可能是银屑病的一个新的治疗靶点。
