期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/ijms23105656
关键词
thalidomide; ER stress; TLR4; inflammation; macrophages; silicosis
资金
- National Natural Science Foundation of China [81972988]
- Natural Science Foundation of Hebei Province [H2020209052]
- Key Research and Development Projects of Hebei Province [192777129D]
Silicosis is the most prevalent occupational disease in China, and currently has no cure. This study found that the drug thalidomide, known for its anti-inflammatory and immunoregulatory effects, has therapeutic potential against silicosis by inhibiting the inflammatory response.
Silicosis is the most prevalent occupational disease in China. It is a form of pulmonary fibrosis caused by the inhalation of silicon particles. As there is no cure for the potentially lethal and progressive condition, the treatment of silicotic fibrosis is an important and difficult problem to address. Thalidomide, a drug with anti-inflammatory and immunoregulatory properties, has been reported to have lung-protective effects. The purpose of this study was to observe the therapeutic effect of thalidomide on silicotic mice and to determine the protective mechanism. By using silicotic mice models and MH-S cells, we found the expression of endoplasmic reticulum stress (ER stress) and Toll-like receptor 4 (TLR4)-nuclear factor kappa-B (NF-kappa B) pathway as well as inflammation-related factors were upregulated in the macrophages of silicotic mice. The same indexes were detected in silica-stimulated MH-S cells, and the results were consistent with those in vivo. That is, silica activated ER stress and the TLR4-NF-kappa B pathway as well as the inflammatory response in vitro. Treating both silicotic mice and silica-stimulated MH-S cells with thalidomide inhibited ER stress and the TLR4-NF-kappa B pathway as well as the inflammatory response. The present study demonstrates thalidomide as a potential therapeutic agent against silicosis.
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