Tiotropium/Olodaterol Reduce Cigarette Smoking Extract-induced Cell Death in BEAS-2B Bronchial Epithelial Cells

Abstract Background: 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; 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.Methods: Cell 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.Results: Tiotropium/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.Conclusions: CSE 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.

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Tiotropium/Olodaterol treatment reduces cigarette smoke extract-induced cell death in BEAS-2B bronchial epithelial cells

BMC Pharmacology and Toxicology ◽

10.1186/s40360-020-00451-0 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Cheng-hsiung Chen ◽

Yi-Rong Li ◽

Sheng-Hao Lin ◽

Hsiu-Hui Chang ◽

Woei-Horng Chai ◽

...

Keyword(s):

Cell Death ◽

Epithelial Cells ◽

Cigarette Smoke ◽

Cell Injury ◽

Underlying Mechanism ◽

Cigarette Smoke Extract ◽

Bronchial Epithelial Cells ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Jnk Activation

Abstract Background 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; 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. Methods Cell 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. Results Tiotropium/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. Conclusions CSE 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.

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Tiotropium/Olodaterol Reduce Cigarette Smoking Extract-induced Cell Death in BEAS-2B Bronchial Epithelial Cells

10.21203/rs.3.rs-22369/v2 ◽

2020 ◽

Author(s):

Cheng-Hsiung Chen ◽

Yi-Rong Li ◽

Sheng-Hao Lin ◽

Hsiu-Hui Chang ◽

Woei-Horng Chai ◽

...

Keyword(s):

Cell Death ◽

Epithelial Cells ◽

Cigarette Smoking ◽

Cell Injury ◽

Muscle Relaxation ◽

Bronchial Epithelial Cells ◽

Airflow Limitation ◽

Special Focus ◽

Short Term Treatment ◽

Bronchial Epithelial

Abstract Background: COPD is characterized by progressive irreversible airflow limitation. Cigarette smoking is an important risk factor for destruction of lung parenchyma or emphysema. Disruption of epithelial layer integrity may contribute to lung injury in response to CS exposure. Tiotropium/Olodaterol act as bronchodilator to treatment COPD by preventing ASM contraction and muscle relaxation; however, the effect of dual bronchodilator on epithelial cell injury and its underlying mechanism is still unclear. Methods: In this study, we aim to evaluate the effect of Tiotropium/Olodaterol on CSE-mediate cell death, with a special focus on autophagy. In this study, we investigated the effects of Tiotropium/Olodaterol on cell viability, the mitochondrial membrane potential (MMP; Δφm), and autophagy in BEAS-2B bronchial epithelial cells. Results: Tiotropium/olodaterol significantly inhibit CSE-induce cell death, mitochondria dysfunction and autophagy in response to short-term treatment with CSE. Moreover, decrease in ERK and JNK activation after CSE treatment were reversed by Tiotropium/olodaterol treatment. Conclusions: Tiotropium/olodaterol have protective effect against CSE-induced cell death which may related to induction of autophagy via activating ERK and JNK. In this study, we provide a possible novel mechanism for dual-bronchodilator in COPD treatment.

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Tiotropium/Olodaterol Reduce Cigarette Smoking Extract-induced Cell Death in BEAS-2B Bronchial Epithelial Cells

10.21203/rs.3.rs-22369/v1 ◽

2020 ◽

Author(s):

Cheng-Hsiung Chen ◽

Yi-Rong Li ◽

Sheng-Hao Lin ◽

Hsiu-Hui Chang ◽

Woei-Horng Chai ◽

...

Keyword(s):

Cell Death ◽

Epithelial Cells ◽

Cigarette Smoking ◽

Cell Injury ◽

Muscle Relaxation ◽

Bronchial Epithelial Cells ◽

Airflow Limitation ◽

Special Focus ◽

Short Term Treatment ◽

Bronchial Epithelial

Abstract Background COPD is characterized by progressive irreversible airflow limitation. Cigarette smoking is an important risk factor for destruction of lung parenchyma or emphysema. Disruption of epithelial layer integrity may contribute to lung injury in response to CS exposure. Tiotropium/Olodaterol act as bronchodilator to treatment COPD by preventing ASM contraction and muscle relaxation; however, the effect of dual bronchodilator on epithelial cell injury and its underlying mechanism is still unclear. In this study, we aim to evaluate the effect of Tiotropium/Olodaterol on CSE-mediate cell death, with a special focus on autophagy.Methods In this study, we investigated the effects of Tiotropium/Olodaterol on cell viability, the mitochondrial membrane potential (MMP; Δφm), and autophagy in BEAS-2B bronchial epithelial cells. Result: Tiotropium/olodaterol significantly inhibit CSE-induce cell death, mitochondria dysfunction and autophagy in response to short-term treatment with CSE. Moreover, decrease in ERK and JNK activation after CSE treatment were reversed by Tiotropium/olodaterol treatment. Conclusion: Tiotropium/olodaterol have protective effect against CSE-induced cell death which may related to induction of autophagy via activating ERK and JNK. In this study, we provide a possible novel mechanism for dual bronchodilator in COPD treatment.

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Cigarette smoke activates the parthanatos pathway of cell death in human bronchial epithelial cells

Cell Death Discovery ◽

10.1038/s41420-019-0205-3 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 6

Author(s):

Lisa Künzi ◽

Gregory E. Holt

Keyword(s):

Cell Death ◽

Epithelial Cells ◽

Cigarette Smoke ◽

Bronchial Epithelial Cells ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial

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Calcium-dependent and independent mechanisms of capsaicin receptor (TRPV1)-mediated cytokine production and cell death in human bronchial epithelial cells

Journal of Biochemical and Molecular Toxicology ◽

10.1002/jbt.20084 ◽

2005 ◽

Vol 19 (4) ◽

pp. 266-275 ◽

Cited By ~ 52

Author(s):

Christopher A. Reilly ◽

Mark E. Johansen ◽

Diane L. Lanza ◽

Jeewoo Lee ◽

Ju-Ok Lim ◽

...

Keyword(s):

Cell Death ◽

Epithelial Cells ◽

Cytokine Production ◽

Bronchial Epithelial Cells ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Capsaicin Receptor ◽

Calcium Dependent

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Additive effects of simulated microgravity and ionizing radiation in cell death, induction of ROS and expression of RAC2 in human bronchial epithelial cells

npj Microgravity ◽

10.1038/s41526-020-00123-7 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Shaobo Tan ◽

Weiwei Pei ◽

Hao Huang ◽

Guangming Zhou ◽

Wentao Hu

Keyword(s):

Cell Death ◽

Epithelial Cells ◽

Ionizing Radiation ◽

Simulated Microgravity ◽

Biological Effects ◽

Bronchial Epithelial Cells ◽

Space Environment ◽

Mechanistic Study ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial

Abstract Radiation and microgravity are undoubtedly two major factors in space environment that pose a health threat to astronauts. However, the mechanistic study of their interactive biological effects is lacking. In this study, human lung bronchial epithelial Beas-2B cells were used to study the regulation of radiobiological effects by simulated microgravity (using a three-dimensional clinostat). It was found that simulated microgravity together with radiation induced drop of survival fraction, proliferation inhibition, apoptosis, and DNA double-strand break formation of Beas-2B cells additively. They also additively induced Ras-related C3 botulinum toxin substrate 2 (RAC2) upregulation, leading to increased NADPH oxidase activity and increased intracellular reactive oxygen species (ROS) yield. The findings indicated that simulated microgravity and ionizing radiation presented an additive effect on cell death of human bronchial epithelial cells, which was mediated by RAC2 to some extent. The study provides a new perspective for the better understanding of the compound biological effects of the space environmental factors.

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