Recillas-Román Stephanie, Montaño Martha, Ruiz Víctor, Pérez-Ramos Julia, Becerril Carina, Herrera Iliana, Amador-Muñoz Omar, Martínez-Domínguez Y Margarita, Ramos Carlos
Doctorate in Biological and Health Sciences, 27789Metropolitan Autonomous University-Xochimilco (UAM-X), Mexico City, Mexico.
Cell Biology Laboratory, Department of Research in Pulmonary Fibrosis, 42635National Institute of Respiratory Diseases Ismael Cosío Villegas (INER), Mexico City, Mexico.
Int J Toxicol. 2021 Dec;40(6):506-516. doi: 10.1177/10915818211044809. Epub 2021 Sep 16.
Wood smoke (WS) contains many harmful compounds, including polycyclic aromatic hydrocarbons (PAHs). WS induces inflammation in the airways and lungs and can lead to the development of various acute and chronic respiratory diseases. Pulmonary fibroblasts are the main cells involved in the remodeling of the extracellular matrix (ECM) during the WS-induced inflammatory response. Although fibroblasts remain in a low proliferation state under physiological conditions, they actively participate in ECM remodeling during the inflammatory response in pathophysiological states. Consequently, we used normal human lung fibroblasts (NHLFs) to assess the potential effects of the PAHs-containing wood smoke extract (WSE) on the growth rate, total collagen synthesis, and the expression levels of collagen I and III, matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, and the transforming growth factor (TGF)-β1. We also assessed MMPs activity. The results showed that WSE induced a trimodal behavior in the growth rate curves in NHLFs; the growth rate increased with 0.5-1 % WSE and decreased with 2.5% WSE, without causing cell damage; 5-20% WSE inhibited the growth and induced cell damage. After 3 hours of exposure, 2.5% WSE induced an increase in total collagen synthesis and upregulation of TGF-β1, collagen I and III, MMP-1, TIMP-1, and TIMP-2 expression. However, MMP-2 expression was downregulated and MMP-9 was not expressed. The gelatinase activity of MMP-2 was also increased. These results suggest that WSE affects the ECM remodeling in NHLFs and indicate the potential involvement of PAHs in this process.
木烟(WS)含有许多有害化合物,包括多环芳烃(PAHs)。木烟可诱发气道和肺部炎症,并可能导致各种急慢性呼吸道疾病的发生。肺成纤维细胞是木烟诱导的炎症反应过程中参与细胞外基质(ECM)重塑的主要细胞。尽管成纤维细胞在生理条件下处于低增殖状态,但在病理生理状态下的炎症反应过程中,它们会积极参与ECM重塑。因此,我们使用正常人肺成纤维细胞(NHLFs)来评估含多环芳烃的木烟提取物(WSE)对生长速率、总胶原蛋白合成以及I型和III型胶原蛋白、基质金属蛋白酶(MMP)-1、MMP-2、MMP-9、金属蛋白酶组织抑制剂(TIMP)-1、TIMP-2和转化生长因子(TGF)-β1表达水平的潜在影响。我们还评估了基质金属蛋白酶的活性。结果表明,WSE在NHLFs的生长速率曲线中诱导出一种三峰行为;0.5-1%的WSE使生长速率增加,2.5%的WSE使其降低,但未造成细胞损伤;5-20%的WSE抑制生长并诱导细胞损伤。暴露3小时后,2.5%的WSE诱导总胶原蛋白合成增加以及TGF-β1、I型和III型胶原蛋白、MMP-1、TIMP-1和TIMP-2表达上调。然而,MMP-2表达下调,MMP-9未表达。MMP-2的明胶酶活性也增加。这些结果表明,WSE影响NHLFs中的ECM重塑,并表明多环芳烃可能参与了这一过程。