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Extracellular Histones Promote Pulmonary Fibrosis in Patients With Coal Workers’ Pneumoconiosis

Zhang, Yanlin, MD; Guan, Li, MD; Zheng, Yimu, MD; Mao, Lijun, MD; Li, Shuqiang, MD; Zhao, Jinyuan, MD

Journal of Occupational and Environmental Medicine: February 2019 - Volume 61 - Issue 2 - p 89–95
doi: 10.1097/JOM.0000000000001473

Objective: This investigation assessed the profibrotic role that extracellular histones play in the pathogenesis of coal workers’ pneumoconiosis (CWP).

Methods: The correlation of extracellular histones with small opacity profusion (SOP) and transforming growth factor-β (TGF-β) was analyzed. The stimulating effect of extracellular histones on pulmonary fibroblast was assessed in vitro.

Results: The levels of extracellular histones in plasma were positively correlated with SOP and TGF-β in the coal miners investigated. Plasma collected from patients with CWP caused apparent lung fibroblast proliferation, while anti-H4 antibody antagonized the stimulating effect of the patient plasma by blocking histone H4. In vitro experiments showed that extracellular histones directly stimulated fibroblast proliferation.

Conclusion: Consistent with our hypothesis, the concentrations of extracellular histones were indices of the severity of pulmonary fibrosis in simple CWP, and extracellular histones-targeted intervention could inhibit the proliferation of lung fibroblast.

Peking University Third Hospital, Research Center of Occupational Medicine, Beijing, China.

Address correspondence to: Shuqiang Li, MD, No. 49 North Garden Road, Haidian District, Beijing 100191, People's Republic of China (; Jinyuan Zhao, No. 49 North Garden Road, Haidian District, Beijing 100191, People's Republic of China (

Funding for this study was provided by National Natural Science Foundation of China (grant nos. 81773374, 81641119), Beijing, People's Republic of China; Natural Science Foundation of Beijing Municipality (grant no. 7182179), Beijing, People's Republic of China; Start-up fund for excellent returnee of Peking University Third Hospital (grant no. Y75513–05), Beijing, People's Republic of China; National clinical key specialty project fund of China (occupational medicine), Beijing, People's Republic of China.

Li, Zhang, Guan, Zheng, Mao, and Zhao have no relationships/conditions/circumstances that present potential conflict of interest.

The JOEM editorial board and planners have no financial interest related to this research.

Copyright © 2019 by the American College of Occupational and Environmental Medicine