Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish Center for Education and Research, Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China.
Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
Sci Total Environ. 2023 Sep 20;892:164732. doi: 10.1016/j.scitotenv.2023.164732. Epub 2023 Jun 7.
Short-term high-concentration exposure to airborne fine particulate matter (PM) is strongly associated with the risk of acute lung injury (ALI). It has been recently reported that exosomes (Exos) involve in the progression of respiratory diseases. However, the molecular mechanisms by which exosome-mediated intercellular signaling exacerbate PM-induced ALI remains largely unaddressed. In the present study, we firstly investigated the effect of macrophage-derived exosomal tumor necrosis factor α (TNF-α) on pulmonary surfactant proteins (SPs) expression in epithelial MLE-12 cells after PM exposure. The higher levels of exosomes in the bronchoalveolar lavage fluid (BALF) of PM-induced ALI mice were found. BALF-exosomes significantly up-regulated SPs expression in MLE-12 cells. Moreover, we found that remarkably high expression of TNF-α in exosomes secreted by PM-treated RAW264.7 cells. Exosomal TNF-α promoted thyroid transcription factor-1 (TTF-1) activation and SPs expression in MLE-12 cells. Furthermore, intratracheal instillation of macrophage-derived TNF-α-containing exosomes increased epithelial cell SPs expression in the lungs of mice. Taken together, these results suggest that macrophages-secreted exosomal TNF-α can trigger epithelial cell SPs expression, which provides new insight and potential target in the mechanism of epithelial cell dysfunction in PM-induced ALI.
短期高浓度暴露于空气中的细颗粒物（PM）与急性肺损伤（ALI）的风险密切相关。最近有报道称，外泌体（Exos）参与了呼吸系统疾病的进展。然而，外泌体介导的细胞间信号转导加剧 PM 诱导的 ALI 的分子机制在很大程度上尚未得到解决。在本研究中，我们首先研究了巨噬细胞来源的外泌体肿瘤坏死因子-α（TNF-α）在 PM 暴露后对上皮细胞 MLE-12 中肺表面活性蛋白（SP）表达的影响。在 PM 诱导的 ALI 小鼠的支气管肺泡灌洗液（BALF）中发现了更高水平的外泌体。BALF 外泌体显著上调 MLE-12 细胞中 SPs 的表达。此外，我们发现 PM 处理的 RAW264.7 细胞分泌的外泌体中 TNF-α 的表达显著升高。外泌体 TNF-α促进 MLE-12 细胞中甲状腺转录因子-1（TTF-1）的激活和 SPs 的表达。此外，气管内滴注巨噬细胞来源的含 TNF-α 的外泌体增加了小鼠肺部上皮细胞 SPs 的表达。综上所述，这些结果表明巨噬细胞分泌的外泌体 TNF-α可以触发上皮细胞 SPs 的表达，为 PM 诱导的 ALI 中上皮细胞功能障碍的机制提供了新的见解和潜在靶点。
