由于高水平的自由基，香烟烟雾是氧化应激的主要原因之一，这反过来又导致肺泡细胞壁的降解和肺气肿的发展。吸烟与慢性支气管炎有关，慢性阻塞性肺疾病（COPD）和肺癌。本研究的目的是观察香烟烟雾提取物（CSE）对A549细胞系中TNF-α和MMPs介导的粘液高分泌的影响。MTT实验显示CSE引起A549细胞活力水平的剂量依赖性下降。此外,AO/PI和MitotrackerRed染色实验证明CSE导致A549细胞发生凋亡。这是通过观察线粒体膜电位的降低来确定的。CSE被发现负责细胞内ROS的形成，通过荧光显微镜DCFDA染色观察。在20%CSE暴露的细胞中,约65%的迁移率降低。CSE暴露导致TNF-αmRNA水平显著升高,与对照细胞相比,MMP-7和MMP-12。此外,MUC5AC和MUC5B的表达也由CSE引起。人上皮细胞受到TNF-α和MMPs分泌粘液的刺激,如MUC5AC和MUC5B的表达所示。CSE可以通过TNF-α和MMPs介导的途径诱导肺粘液。
Cigarette smoke is one of the leading causes of oxidative stress due to high levels of free radicals, which in turn leads to the degradation of alveolar cell walls and development of emphysema. Cigarette smoking has been linked to chronic bronchitis, Chronic Obstructive Pulmonary Disease (COPD) and lung cancer as well. The aim of the present
study was to observe the effect of cigarette smoke extract (CSE) on TNF-α and MMPs mediated mucus hypersecretion in A549 cell line. The MTT experiments showed that CSE caused a dose-dependent decline in the level of viability of A549 cells. In addition, AO/PI and Mitotracker Red staining assays demonstrated that CSE caused the A549 cells to undergo apoptosis. This was determined by observing the reduction in mitochondrial membrane potential. CSE was found to be responsible for the formation of intracellular ROS, which was observed by DCFDA staining through fluorescence microscopy. Approximately 65% migration rate was decreased in 20% CSE exposed cells. CSE exposure led to the significantly increased mRNA levels of TNF-α, MMP-7, and MMP-12, in comparison to the control cells. Additionally, the expression of MUC5AC and MUC5B was provoked by CSE as well. Human epithelial cells are stimulated by TNF-α and MMPs secreted mucus, as shown by expression of MUC5AC and MUC5B. CSE could induce mucus in lungs through TNF-α and MMPs mediated pathways.
