Silica particles disorganize the polarization of pulmonary macrophages in mice.

Abstract

Silicosis is a fatal fibrotic lung disease caused by long-term silica particle exposure, in which pulmonary macrophages play an important role. However, the relationship between macrophage polarization and silicosis remains unclear. We established an experimental silicosis mouse model to investigate macrophage polarization during silicosis development. C57BL/c mice were exposed to silica by intra-tracheal instillation and sacrificed at different time points. Lung tissues and bronchoalveolar lavage fluid were collected for flow cytometry, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assays, western blotting, and histology examinations. The polarization of pulmonary macrophages was dysregulated during silicosis development. In the early stage of silicosis, M1 macrophages were induced and played a leading role in eliciting inflammatory; in the late stage, M2 macrophages were induced to promote tissue repair. Levels of several cytokines in lung tissue microenvironment changed with macrophage polarization. Inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-1β and IL-6 were upregulated in the inflammation stage, while the anti-inflammatory cytokine IL-10 was upregulated in the fibrosis stage. Furthermore, we found that STAT (signal transducer and activator of transcription) and IRF (interferon regulatory factor) signaling pathway were involved in the regulation of macrophage polarization in silicosis. In summary, macrophage polarization is closely related to the occurrence and development of silicosis and may be a key point for further elucidating silicosis pathogenesis.

• Authors: Youliang Zhao, Changfu Hao, Lei Bao, Di Wang, Yiping Li, Yaqian Qu, Mingcui Ding, Ahui Zhao, Wu Yao
• Journal: Ecotoxicology and environmental safety (Ecotoxicol Environ Saf) Vol. 193 Pg. 110364 (Apr 15 2020) ISSN: 1090-2414 [Electronic] Netherlands
• PMID: 32114243 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Interferon Regulatory Factors
• STAT Transcription Factors
• Silicon Dioxide

Topics

• Animals
• Bronchoalveolar Lavage Fluid
• Cytokines (metabolism)
• Inflammation (immunology, metabolism, pathology)
• Interferon Regulatory Factors (metabolism)
• Lung (immunology, metabolism, pathology)
• Macrophages, Alveolar (drug effects, immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Pulmonary Fibrosis (metabolism)
• STAT Transcription Factors (metabolism)
• Silicon Dioxide
• Silicosis (immunology, metabolism, pathology)