Theranostics 2019; 9(7):1878-1892. doi:10.7150/thno.29682

Research Paper

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

Sitong Du1*, Chao Li1*, Yiping Lu1, Xue Lei1, Yiting Zhang1, Siyi Li1, Fangwei Liu1, Ying Chen1, Dong Weng1,2, Jie Chen1✉

1. Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, PR China.
2. Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, PR China.
*Equal contribution to this study

Abstract

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.

Keywords: crystalline silica, dioscin, macrophage, autophagy, mitochondrial dysfunction

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Du S, Li C, Lu Y, Lei X, Zhang Y, Li S, Liu F, Chen Y, Weng D, Chen J. Dioscin Alleviates Crystalline Silica-Induced Pulmonary Inflammation and Fibrosis through Promoting Alveolar Macrophage Autophagy. Theranostics 2019; 9(7):1878-1892. doi:10.7150/thno.29682. Available from http://www.thno.org/v09p1878.htm