Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages

Mei-yue Song1,2,3, Jia-xin Wang4, You-liang Sun5, Zhi-fa Han6, Yi-tian Zhou7,8,9, Ying Liu7, Tian-hui Fan7, Zhao-guo Li1, Xian-mei Qi7, Ya Luo7, Pei-ran Yang7, Bai-cun Li7, Xin-ri Zhang1,1, Jing Wang7, Chen Wang7
1 .Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan 030001, China
2 Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China
3 National Clinical Research Center for Respiratory Diseases, Beijing 100029, China
4 Tsinghua-Peking Center for Life Sciences, Department of Biology, College of Medicine, Tsinghua University, Beijing 100084, China
5 School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China
6 Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China
7 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100730, China
8 Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
9 Peking Union Medical College, MD Program, Beijing 100730, China
Correspondence to: Xin-ri Zhang:, Jing Wang:, Chen Wang:,
DOI: 10.1038/s41401-021-00693-6
Received: 28 December 2020
Accepted: 7 May 2021
Advance online: 20 August 2021


Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat silicosis. Tetrandrine is the only drug approved for silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown. Here, in this study, we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration. To this end, we used multiple cardiopulmonary function test, as well as markers for inflammation and fibrosis. Moreover, using single cell RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from silicosis and control mice, our results provide a novel description of the target pathways for tetrandrine. Specifically, we found that tetrandrine attenuated silicosis by inhibiting both the canonical and non-canonical NLRP3 inflammasome pathways in lung macrophages. Taken together, our work showed that tetrandrine yielded promising results against silicosis-associated inflammation and fibrosis and further lied the groundwork for understanding its molecular targets. Our results also facilitated the wider adoption and development of tetrandirne, potentially accelerating a globally accepted therapeutic strategy for silicosis.
Keywords: tetrandrine; silicosis; macrophages; NLRP3 inflammasome; lung function

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