Medical Research Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province 450052, China.
Department of Orthopedics, Zhengzhou Central Hospital, Zhengzhou, Henan Province 450052, China.
Life Sci. 2019 Jul 15;229:46-56. doi: 10.1016/j.lfs.2019.05.030. Epub 2019 May 11.
Tumor growth is an angiogenesis-dependent process that requires sustained new vessel growth. Interleukin-17 (IL-17A) is a key cytokine that modulates tumor progression. However, whether IL-17A affects the metabolism of endothelial cells is unknown.
A xenograft model was established by implanting H460 (human lung cancer cell line) cells transfected with IL-17A-expressing or control vector. The effects of IL-17A on sprouting and tube formation of human umbilical vein endothelial cells (HUVECs) were measured. After treatment with IL-17A, the proliferation and migration of HUVECs were examined. Liquid chromatography-mass spectrometry (LC-MS) and Seahorse were used to detect the effects of IL-17A on mitochondrial respiration and fatty acid β-oxidation (FAO) in HUVECs. Western blotting was used to examine signaling pathways.
Herein, we found that IL-17A promoted H460 tumor growth and angiogenesis in vivo and in vitro. Moreover, IL-17A stimulated angiogenesis by enhancing FAO, increasing mitochondrial respiration of endothelial cells. The AMP-activated protein kinase (AMPK) signaling pathway was activated to promote FAO. Finally, IL-17A-induced angiogenesis was blocked when FAO was inhibited using etomoxir.
In summary, these results indicate that IL-17A stimulates angiogenesis by promoting FAO. Thus, our study might provide a new therapeutic target for angiogenic vascular disorders.
肿瘤生长是一个依赖血管生成的过程，需要持续的新血管生长。白细胞介素-17（IL-17A）是调节肿瘤进展的关键细胞因子。然而，IL-17A 是否影响内皮细胞的代谢尚不清楚。
通过植入转染有表达 IL-17A 或对照载体的 H460（人肺癌细胞系）细胞，建立异种移植模型。测量 IL-17A 对人脐静脉内皮细胞（HUVEC）发芽和管形成的影响。用 IL-17A 处理后，检查 HUVEC 的增殖和迁移。使用液相色谱-质谱（LC-MS）和 Seahorse 检测 IL-17A 对 HUVEC 线粒体呼吸和脂肪酸 β-氧化（FAO）的影响。使用 Western blot 检测信号通路。
在此，我们发现 IL-17A 促进体内和体外 H460 肿瘤生长和血管生成。此外，IL-17A 通过增强内皮细胞的 FAO 来刺激血管生成，增加内皮细胞的线粒体呼吸。激活 AMP 激活的蛋白激酶（AMPK）信号通路以促进 FAO。最后，当使用 etomoxir 抑制 FAO 时，IL-17A 诱导的血管生成被阻断。
总之，这些结果表明，IL-17A 通过促进 FAO 来刺激血管生成。因此，我们的研究可能为血管生成性血管疾病提供新的治疗靶点。
