Journal Article

Dioscin Alleviates Crystalline Silica-Induced Pulmonary Inflammation and Fibrosis through Promoting Alveolar Macrophage Autophagy

Li, Siyi, Lei, Xue, Lu, Yiping, Liu, Fangwei, Chen, Ying, Du, Sitong, Li, Chao, Zhang, Yiting, Chen, Jie, Weng, Dong

2019

Overview

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. We established experimental model of silicosis with wildtype and Atg5 Dppa3 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. 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 Atg5 Dppa3 mice. 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.

• Publisher: Ivyspring International Publisher
• Subject: Animals / Apoptosis - drug effects / Autophagy - drug effects / Cell Line / Cell Survival - drug effects / Diosgenin - analogs & derivatives / Diosgenin - pharmacology / Female / Macrophages - drug effects / Macrophages - metabolism / Macrophages, Alveolar - drug effects / Macrophages, Alveolar - metabolism / Mice / Mice, Inbred C57BL / Mitochondria - drug effects / Mitochondria - metabolism / Oxidative Stress - drug effects / Pneumonia - chemically induced / Pneumonia - drug therapy / Pneumonia - metabolism / Pulmonary Fibrosis - drug therapy / Pulmonary Fibrosis - metabolism / Reactive Oxygen Species - metabolism / Research Paper / Silicon Dioxide - pharmacology / Silicosis - drug therapy / Silicosis - metabolism