Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, PR China.
Translational Medicine Center, Beijing Chest Hospital, Capital Medical University, Beijing 101149, PR China; Beijing Key Laboratory in Drug Resistant Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, PR China.
Sci Total Environ. 2022 Aug 20;835:155357. doi: 10.1016/j.scitotenv.2022.155357. Epub 2022 Apr 19.
As air pollution has been paid more attention to by public in recent years, effects and mechanism in particulate matter-triggered health problems become a focus of research. Lysosomes and mitochondria play an important role in regulation of inflammation. Interleukin-33 (IL-33) has been proved to promote inflammation in our previous studies. In this research, macrophage cell line RAW264.7 was used to explore the potential mechanism of upregulation of IL-33 induced by 1,4-naphthoquinone black carbon (1,4-NQ-BC), and to explore changes of lysosomes and mitochondria during the process.
50 μg/mL 1,4-NQ-BC exposure for 24 h dramatically increased expression of IL-33 in RAW264.7 cells. Lysosomal membrane permeability was damaged by 1,4-NQ-BC treatment, and higher mitochondrial membrane potential and ROS level were induced by 1,4-NQ-BC. The results of proteomics suggested that expression of ferritin light chain was increased after cells were challenged with 1,4-NQ-BC, and it was verified by Western blot. Meanwhile, expressions of p62 and LC3B-II were increased by 50 μg/mL 1,4-NQ-BC in RAW264.7 cells. Ultimately, expression of IL-33 could return to same level as control in cells treated with 50 μg/mL 1,4-NQ-BC and 50 μM deferoxamine combined.
1,4-NQ-BC induces IL-33 upregulation in RAW264.7 cells, and it is responsible for higher lysosomal membrane permeability and ROS level, lower mitochondrial membrane potential, and inhibition of autophagy. Ferritin light chain possibly plays an important role in the upregulation of IL-33 evoked by 1,4-NQ-BC.
近年来，随着公众对空气污染的关注度不断提高，颗粒物引发健康问题的影响和机制成为研究的焦点。溶酶体和线粒体在炎症调节中起着重要作用。白细胞介素-33（IL-33）在我们之前的研究中已被证明能促进炎症。在这项研究中，使用巨噬细胞 RAW264.7 细胞系来探索 1,4-萘醌黑碳（1,4-NQ-BC）诱导的 IL-33 上调的潜在机制，并探讨在此过程中溶酶体和线粒体的变化。
50μg/ml 1,4-NQ-BC 暴露 24 小时可显著增加 RAW264.7 细胞中 IL-33 的表达。1,4-NQ-BC 处理破坏溶酶体膜通透性，并诱导更高的线粒体膜电位和 ROS 水平。蛋白质组学的结果表明，细胞受到 1,4-NQ-BC 刺激后铁蛋白轻链表达增加，并用 Western blot 验证。同时，50μg/ml 1,4-NQ-BC 处理 RAW264.7 细胞后，p62 和 LC3B-II 的表达增加。最终，用 50μg/ml 1,4-NQ-BC 和 50μM 去铁胺联合处理细胞，IL-33 的表达可恢复到对照水平。
1,4-NQ-BC 诱导 RAW264.7 细胞中 IL-33 的上调，这与其引起的更高的溶酶体膜通透性和 ROS 水平、更低的线粒体膜电位和自噬抑制有关。铁蛋白轻链可能在 1,4-NQ-BC 诱导的 IL-33 上调中发挥重要作用。
