Abstract
BackgroundCigarette smoking is a critical risk factor for the destruction of lung parenchyma or the development of emphysema, which is characteristic of COPD. Disruption of epithelial layer integrity may contribute to lung injury following cigarette smoke extract (CSE) exposure. Tiotropium/olodaterol acts as a bronchodilator for COPD treatment; however, the effect of dual bronchodilators on epithelial cell injury and its underlying mechanism remain unclear. In this study, we evaluated the effect of tiotropium/olodaterol on CSE-mediated cell death and the underlying mechanisms.MethodsCell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis, necrosis, and autophagy were evaluated using flow cytometry. Autophagy-related protein, phosphorylated ERK, expression was determined using Western blotting.ResultsTiotropium/olodaterol significantly inhibited CSE-induced cell death, mitochondria dysfunction, and autophagy, which had no significant effect on apoptosis or necrosis in BEAS-2B human bronchial epithelial cells. Moreover, tiotropium/olodaterol attenuated CSE-induced upregulation of JNK.ConclusionsCSE induced cell death and caused consistent patterns of autophagy and JNK activation in BEAS-2B human bronchial epithelial cells. Tiotropium/olodaterol treatment protected bronchial epithelial cells from CSE-induced injury and inhibited activation of autophagy and upregulation of JNK phosphorylation. These results indicate that tiotropium/olodaterol may protect epithelial cells from the deleterious effects of CSE exposure, which is associated with the regulation of autophagy and JNK activation.
Highlights
Cigarette smoking is a critical risk factor for the destruction of lung parenchyma or the development of emphysema, which is characteristic of chronic obstructive pulmonary disease (COPD)
cigarette smoke extract (CSE) induces death in BEAS-2B bronchial epithelial cells To evaluate the effect of CSE on BEAS-2B bronchial epithelial cells, BEAS-2B cells were exposed to various dosages of CSE
These results indicate that CSE treatment considerably increased bronchial cell injury at a dose greater than 5% CSE
Summary
Cigarette smoking is a critical risk factor for the destruction of lung parenchyma or the development of emphysema, which is characteristic of COPD. Disruption of epithelial layer integrity may contribute to lung injury following cigarette smoke extract (CSE) exposure. Tiotropium/olodaterol acts as a bronchodilator for COPD treatment; the effect of dual bronchodilators on epithelial cell injury and its underlying mechanism remain unclear. We evaluated the effect of tiotropium/olodaterol on CSE-mediated cell death and the underlying mechanisms. Cigarette smoking is known to induce cell death in lung structural cells, which contribute to the development of pulmonary emphysema in the lungs of smokers [4, 5]. The underlying mechanism of CS extract (CSE)-induced cell death remains unclear, despite evidence suggesting that cell death plays a crucial role in emphysema and COPD development. Protecting bronchial epithelial cells against CS-induced alterations is paramount
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