Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Republic of Korea; College of Veterinary Medicine and BK21 FOUR Program, Chungnam National University, Daejeon, Republic of Korea.
Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Republic of Korea; College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, Republic of Korea.
Food Chem Toxicol. 2024 Jan;183:114201. doi: 10.1016/j.fct.2023.114201. Epub 2023 Nov 25.
Exposure to particulate matter is currently recognized as a serious aggravating factor of respiratory diseases. In this study, we investigated the effects of particulate matter (PM) on the respiratory system in BALB/c mice and NCI-H292 cells. PM (0, 2.5, 5 and 20 mg/kg) was administered to mice by intra-tracheal instillation for 7 days. After a 7 day-repeated treatment of PM, we evaluated inflammatory cytokines/cell counts in bronchoalveolar lavage fluid (BALF) and conducted pulmonary histology and functional test. We also investigated the role of TXNIP/NF-κB and SIRT1-mediated p53 and TGF-β/Smad3 pathways in PM-induced airway inflammation and pulmonary dysfunction. PM caused a significant increase in pro-inflammatory cytokines, inflammatory cell counts in bronchoalveolar lavage fluid. PM-mediated oxidative stress down-regulated thioredoxin-1 and up-regulated thioredoxin-interacting protein and activation of nuclear factor-kappa B in the lung tissue and PM-treated NCI-H292 cells. PM suppressed sirtuin1 protein levels and increased p53 acetylation in PM-exposed mice and PM-treated NCI-H292 cells. In addition, PM caused inflammatory cell infiltration and the thickening of alveolar walls by exacerbating the inflammatory response in the lung tissue. PM increased levels of transforming growth factor-β, phosphorylation of Smad3 and activation of α-smooth muscle actin, and collagen type1A2 in PM-exposed mice and PM-treated NCI-H292 cells. In pulmonary function tests, PM exposure impaired pulmonary function resembling pulmonary fibrosis, characterized by increased resistance and elastance of the respiratory system, and resistance, elastance, and damping of lung tissues, whereas decreased compliance of the respiratory system, forced expired volume and forced vital capacity. Overall, PM-mediated oxidative stress caused airway inflammation and pulmonary dysfunction with pulmonary fibrosis via TXNIP pathway/NF-κB activation and modulation of the SIRT1-mediated TGF-β/Smad3 pathways. The results of this study can provide fundamental data on the potential adverse effects and underlying mechanism of pulmonary fibrosis caused by PM exposure as a public health concern. Due to the potential toxicity of PM, people with respiratory disease must be careful with PM exposure.
目前，人们已经认识到颗粒物暴露是加重呼吸系统疾病的一个严重因素。在这项研究中，我们研究了颗粒物（PM）对 BALB/c 小鼠和 NCI-H292 细胞呼吸系统的影响。通过气管内滴注，将 PM（0、2.5、5 和 20mg/kg）施用于小鼠，持续 7 天。在 PM 重复处理 7 天后，我们评估了支气管肺泡灌洗液（BALF）中的炎症细胞因子/细胞计数，并进行了肺组织学和功能测试。我们还研究了 TXNIP/NF-κB 和 SIRT1 介导的 p53 和 TGF-β/Smad3 通路在 PM 诱导的气道炎症和肺功能障碍中的作用。PM 导致促炎细胞因子显著增加，BALF 中的炎症细胞计数增加。PM 介导的氧化应激导致肺组织中硫氧还蛋白-1 下调，硫氧还蛋白相互作用蛋白上调，核因子-κB 激活，并在 PM 处理的 NCI-H292 细胞中。PM 抑制 Sirtuin1 蛋白水平，并增加 PM 暴露小鼠和 PM 处理的 NCI-H292 细胞中 p53 的乙酰化。此外，PM 通过加剧肺组织中的炎症反应，导致炎性细胞浸润和肺泡壁增厚。PM 增加了转化生长因子-β、Smad3 磷酸化和α-平滑肌肌动蛋白、胶原 type1A2 的水平，在 PM 暴露的小鼠和 PM 处理的 NCI-H292 细胞中。在肺功能测试中，PM 暴露会损害肺功能，类似于肺纤维化，表现为呼吸系统阻力和弹性增加，以及肺组织阻力、弹性和阻尼增加，而呼吸系统顺应性、用力呼气量和用力肺活量降低。总之，PM 介导的氧化应激通过 TXNIP 通路/NF-κB 激活和 SIRT1 介导的 TGF-β/Smad3 通路导致气道炎症和肺功能障碍，进而导致肺纤维化。这项研究的结果可为 PM 暴露引起的肺纤维化的潜在不良影响和潜在机制提供基础数据，这是一个公共卫生问题。由于 PM 的潜在毒性，患有呼吸系统疾病的人必须小心 PM 的暴露。
