Department of Occupational Health and Occupational Disease, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China.
School of Public Health, Hebei Medical University, Shijiazhuang, Hebei, PR China.
Ecotoxicol Environ Saf. 2020 Apr 15;193:110364. doi: 10.1016/j.ecoenv.2020.110364. Epub 2020 Feb 27.
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.
矽肺是一种由长期二氧化硅颗粒暴露引起的致命纤维化肺部疾病，其中肺巨噬细胞发挥着重要作用。然而，巨噬细胞极化与矽肺之间的关系尚不清楚。我们建立了一个实验性矽肺小鼠模型，以研究矽肺发展过程中巨噬细胞的极化。C57BL/c 小鼠通过气管内滴注暴露于二氧化硅，并在不同时间点处死。收集肺组织和支气管肺泡灌洗液进行流式细胞术、定量逆转录聚合酶链反应、酶联免疫吸附试验、western blot 和组织学检查。在矽肺发展过程中，肺巨噬细胞的极化被失调。在矽肺的早期，诱导 M1 巨噬细胞并发挥诱导炎症的主导作用；在晚期，诱导 M2 巨噬细胞促进组织修复。肺组织微环境中几种细胞因子的水平随巨噬细胞极化而变化。炎症阶段促炎细胞因子如肿瘤坏死因子-α和白细胞介素（IL）-1β和 IL-6 上调，而纤维化阶段抗炎细胞因子如 IL-10 上调。此外，我们发现 STAT（信号转导和转录激活因子）和 IRF（干扰素调节因子）信号通路参与了矽肺中巨噬细胞极化的调节。总之，巨噬细胞极化与矽肺的发生和发展密切相关，可能是进一步阐明矽肺发病机制的关键点。
