Dioscin Alleviates Crystalline Silica-Induced Pulmonary Inflammation and Fibrosis through Promoting Alveolar Macrophage Autophagy
Dioscin Alleviates Crystalline Silica-Induced Pulmonary Inflammation and Fibrosis through Promoting Alveolar Macrophage Autophagy
复制标题
薯蓣皂甙通过促进肺泡巨噬细胞自噬减轻结晶二氧化硅引起的肺部炎症和纤维化
DOI：
10.7150/thno.29682
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发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Chen, Jie
中科院分区：
文献类型：
--
作者：
Du, Sitong;Li, Chao;Chen, Jie
职业暴露于结晶二氧化硅（CS）颗粒导致矽肺，其特征在于慢性炎症和异常组织修复。肺泡巨噬细胞（Alveolar macrophages，AM）在矽肺发病过程中起着重要作用。以前，我们证实薯蓣皂苷通过调节巨噬细胞诱导的先天性免疫应答对矽肺有积极作用。然而，具体的分子机制仍有待发现。研究方法：采用野生型和Atg 5 flox/Atg 5Dppa 3Cre/+小鼠建立矽肺模型，每日口服薯蓣皂苷，观察薯蓣皂苷对巨噬细胞和肺纤维化的影响。以Atg 5沉默的AM细胞系MH-S为研究对象，探讨薯蓣皂苷对巨噬细胞源性炎症的特异性作用及其分子机制。结果：薯蓣皂苷可促进巨噬细胞自噬。薯蓣皂苷触发的AM自噬限制了CS刺激的线粒体活性氧（mtROS）的质量，减少了依赖于细胞凋亡途径的激活，促进了细胞存活。减轻氧化应激导致炎症因子和趋化因子的分泌减少。薯蓣皂苷治疗减轻巨噬细胞源性炎症和随后的异常胶原修复。薯蓣皂苷对Atg 5 flox/Dppa 3Cre/+小鼠的保护作用均减弱。结论：薯蓣皂苷促进自噬，减少CS诱导的AM细胞凋亡和细胞因子的产生，这可能为矽肺的治疗提供了具体的分子机制。
Occupational exposure to crystalline silica (CS) particles leads to silicosis, which is characterized by chronic inflammation and abnormal tissue repair. Alveolar macrophages (AMs) play a crucial role in the process of silicosis. Previously, we demonstrated positive effect of dioscin on silicosis through modulating macrophage-elicited innate immune response. However, the concrete molecular mechanism remains to be discovered. Methods: We established experimental model of silicosis with wildtype and Atg5flox/floxDppa3Cre/+ mice and oral administrated dioscin daily to explore the effects of dioscin on macrophages and pulmonary fibrosis. AM cell line MH-S with Atg5 silence was used to explore specific function of dioscin on macrophage-derived inflammation and the underlying molecular mechanism. Results: Dioscin could promote autophagy in macrophages. Dioscin-triggered AMs autophagy limited mitochondrial reactive oxygen species (mtROS) mass stimulated by CS, reduced mitochondria-dependent apoptosis pathway activation and facilitated cell survival. Relieved oxidative stress resulted in decreased secretion of inflammatory factors and chemokines. Dioscin treatment alleviated macrophage-derived inflammation and subsequent abnormal collagen repair. All the dioscin's protective effects were diminished in Atg5flox/floxDppa3Cre/+ mice. Conclusion: Dioscin promoting autophagy leads to reduced CS-induced mitochondria-dependent apoptosis and cytokine production in AMs, which may provide concrete molecular mechanism for the therapy of silicosis.