Department of Occupational and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
Department of Occupational and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
Ecotoxicol Environ Saf. 2023 Dec;268:115693. doi: 10.1016/j.ecoenv.2023.115693. Epub 2023 Nov 16.
Macrophage pyroptosis has recently been involved in some inflammatory and fibrosis diseases, however, the role of macrophage pyroptosis in silica-induced pulmonary fibrosis has not been fully elucidated. In this study, we explored the role of macrophage pyroptosis in silicosis in vivo and in vitro. A mouse model of silicosis was established and mice were sacrificed at 7, 14, and 28 days after exposure of silica. The results revealed that the expression of GSDMD and other pyroptosis-related indicators was up-regulated obviously at 14 days after silica exposure, indicating that silica induced pyroptosis in vivo. In vitro, human monocytic leukemia cells (THP-1) and human lung fibroblasts (MRC-5) were used to detect the relationship between macrophage pyroptosis and lung fibroblasts. It showed that silica increased the levels of GSDMD and other pyroptosis-related indicators remarkably in macrophages and the supernatant of macrophage stimulated by silica could promote the upregulation of fibrosis markers in fibroblasts. However, GSDMD knockdown suppressed silica-induced macrophage pyroptosis and alleviated the upregulation of fibrosis markers in fibroblasts, suggesting the important role of macrophage pyroptosis in the activation of myofibroblasts during the progression of silicosis. Taken together, it showed that silica could induce macrophage pyroptosis and inhibiting macrophage pyroptosis could be a feasible clinical strategy to alleviate silicosis.
巨噬细胞焦亡最近被涉及到一些炎症和纤维化疾病中，然而，巨噬细胞焦亡在二氧化硅诱导的肺纤维化中的作用尚未完全阐明。在本研究中，我们探讨了巨噬细胞焦亡在矽肺中的体内和体外作用。建立了矽肺小鼠模型，并在暴露于二氧化硅后 7、14 和 28 天处死小鼠。结果表明，暴露于二氧化硅后 14 天，GSDMD 表达和其他焦亡相关指标明显上调，表明二氧化硅在体内诱导了焦亡。体外，使用人单核白血病细胞（THP-1）和人肺成纤维细胞（MRC-5）检测巨噬细胞焦亡与肺成纤维细胞之间的关系。结果表明，二氧化硅显著增加了巨噬细胞中 GSDMD 和其他焦亡相关指标的水平，并且由二氧化硅刺激的巨噬细胞的上清液可以促进成纤维细胞中纤维化标志物的上调。然而，GSDMD 敲低抑制了二氧化硅诱导的巨噬细胞焦亡，并减轻了成纤维细胞中纤维化标志物的上调，表明巨噬细胞焦亡在矽肺进展过程中肌成纤维细胞的激活中起重要作用。总之，结果表明二氧化硅可以诱导巨噬细胞焦亡，抑制巨噬细胞焦亡可能是缓解矽肺的一种可行的临床策略。
