在COPD中,IL-17A通过PI3K/AKT/mTOR通路调节气道重塑
Ting Ding1, Shunshun Zhao2, Yanhui Gu2
1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Guizhou, 563003, China. tingding2024@163.com.
介素-17A (IL-17A) 通过PI3K/AKT/mTOR通路抑制巨细胞自,从而促进慢性阻塞性肺病 (COPD) 的气道重塑,导致原体沉积增加和空气流量限制.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 慢性阻塞性肺病 (COPD) 是由于气道和肺组织炎症和结构变化导致的不可逆转的气流限制的特征.
- 干白素-17A (IL-17A) 与COPD呼吸道炎症和原沉积有关.
- 自是一种维护正常细胞功能的关键细胞过程.
研究的目的:
- 研究IL-17A在通过PI3K/AKT/mTOR通路调节巨细胞自的作用.
- 阐明IL-17A介导对COPD中自和原蛋白生产的影响的分子机制.
主要方法:
- 在小鼠中建立了COPD呼吸道改造模型,通过肺功能测试和组织学染色 (HE,Masson) 得到证实.
- 使用ELISA检测IL-17A,IL-6和CCL20;通过传输电子显微镜 (TEM) 观察自细胞 (AP).
- 西方涂抹分析PI3K/AKT/mTOR通路蛋白质,自标志物 (贝克林-1,LC3II/I,P62),原蛋白 (原蛋白I,原蛋白III);免疫光用于LC3同位化;在小鼠支气管纤维细胞 (MBF) 中进行IL-17RA操纵的lentiviral转染.
主要成果:
- 慢性肺炎模型显示IL-17A,IL-6和CCL20增加,自细胞形成减少,PI3K/AKT/mTOR通路激活,原蛋白水平升高.
- 在培养的MBF中,通过IL-17RA过度表达的IL-17A刺激导致PI3K/AKT/mTOR通路激活,自标志物减少和原蛋白生产增加.
- 相反,MBF中的IL-17RA沉默逆转了这些效应,表明IL-17RA在调解IL-17A对自和重塑的影响方面发挥了关键作用.
结论:
- IL-17A通过PI3K/AKT/mTOR通路抑制巨细胞自,在COPD呼吸道重塑中发挥重要作用.
- 这种机制有助于增加原沉积和COPD持续的空气流量限制.
- 针对IL-17A/IL-17RA/PI3K/AKT/mTOR/自轴为COPD提供了一个潜在的治疗策略.
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