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.
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.
Environ Pollut. 2019 Oct;253:507-515. doi: 10.1016/j.envpol.2019.06.096. Epub 2019 Jul 3.
Black carbon (BC) can combine with organic matter and form secondary pollutants known as aged BC. BC and aged BC can cause respiratory system inflammation and induce lesions at relevant sites, but the underlying mechanism has remained unknown. To gain insight into the potential mechanisms, we focused on macrophages and transforming growth factor β-activated kinase 1 (TAK1) which are a crucial factor in inflammation. Our research aims to determine the role of TAK1 in macrophages in pulmonary inflammation induced by particulate matter. In this study, BC and 1,4-naphthoquinone were mixed to model aged BC (1,4NQ-BC) in atmosphere. BC induced mice lung inflammation model, lung macrophage knock-down TAK1 animal model and primary macrophage knock-down TAK1 model were used to explore whether TAK1 in macrophage is a critical role in the process of inflammation. The results showed that the expressions of inflammatory cytokines (IL-1β, IL-6, IL-33) mRNA were significantly increased and the phosphorylation of MAPK and NF-κB signaling pathway related proteins were enhanced in RAW 264.7 cell lines. In vivo studies revealed that the indicators of pulmonary inflammation (pathology, inflammatory cell numbers) and related cytokines (IL-1β, IL-6, IL-33) mRNA expressions in CD11c-Map3k7 animals were significantly lower than wild-type animals after mice were instilled particles. In mice primary macrophages, the expressions of IL-6, IL-33 mRNA were inhibited after TAK1 gene was knock-down. These results unequivocally demonstrated that TAK1 plays a crucial role in BC induced lung inflammation in mice, and we can infer that BC and 1,4NQ-BC cause these inflammatory responses by stimulating pulmonary macrophages.
黑碳（BC）可以与有机物结合形成二次污染物，称为老化的 BC。BC 和老化的 BC 会引起呼吸系统炎症，并在相关部位诱导病变，但潜在的机制尚不清楚。为了深入了解潜在的机制，我们专注于巨噬细胞和转化生长因子β激活激酶 1（TAK1），这是炎症的关键因素。我们的研究旨在确定 TAK1 在巨噬细胞中的作用，以及其在颗粒物引起的肺部炎症中的作用。在这项研究中，BC 和 1,4-萘醌混合模拟大气中的老化 BC（1,4NQ-BC）。使用 BC 诱导的小鼠肺部炎症模型、巨噬细胞敲低 TAK1 动物模型和原代巨噬细胞敲低 TAK1 模型，探讨巨噬细胞中的 TAK1 是否在炎症过程中起关键作用。结果表明，RAW 264.7 细胞系中炎症细胞因子（IL-1β、IL-6、IL-33）mRNA 的表达明显增加，MAPK 和 NF-κB 信号通路相关蛋白的磷酸化增强。体内研究表明，CD11c-Map3k7 动物肺部炎症指标（病理学、炎症细胞数量）和相关细胞因子（IL-1β、IL-6、IL-33）mRNA 的表达明显低于野生型动物，这些动物在肺部被注入颗粒物后。在小鼠原代巨噬细胞中，TAK1 基因敲低后，IL-6、IL-33 mRNA 的表达受到抑制。这些结果明确表明，TAK1 在 BC 诱导的小鼠肺部炎症中发挥关键作用，我们可以推断 BC 和 1,4NQ-BC 通过刺激肺部巨噬细胞引起这些炎症反应。
