Tiotropium/Olodaterol treatment reduces cigarette smoke extract-induced cell death in BEAS-2B bronchial epithelial cells. 2020

Cheng-Hsiung Chen, and Yi-Rong Li, and Sheng-Hao Lin, and Hsiu-Hui Chang, and Woei-Horng Chai, and Po-Chiang Chan, and Ching-Hsiung Lin
Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua, 50006, Taiwan, Republic of China.

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. 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. 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. 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.

UI MeSH Term Description Entries
D001980 Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI. Primary Bronchi,Primary Bronchus,Secondary Bronchi,Secondary Bronchus,Tertiary Bronchi,Tertiary Bronchus,Bronchi, Primary,Bronchi, Secondary,Bronchi, Tertiary,Bronchus,Bronchus, Primary,Bronchus, Secondary,Bronchus, Tertiary
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069447 Tiotropium Bromide A scopolamine derivative and CHOLINERGIC ANTAGONIST that functions as a BRONCHODILATOR AGENT. It is used in the treatment of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. 7-((hydroxybis(2-thienyl)acetyl)oxy)-9,9-dimethyl-3-oxa-9-azoniatricyclo(3.3.1.0(2,4))nonane bromide,BA 679 BR,BA-679 BR,Spiriva,Tiotropium,679 BR, BA,BA679 BR,BR, BA 679,Bromide, Tiotropium
D012906 Smoke Visible gaseous suspension of carbon and other particulate matter emitted from burning substances.
D014026 Nicotiana A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; the dried leaves of Nicotiana tabacum are used for SMOKING. Tobacco Plant,Nicotiana tabacum,Plant, Tobacco,Plants, Tobacco,Tobacco Plants
D016923 Cell Death The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. Death, Cell
D048031 JNK Mitogen-Activated Protein Kinases A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION. jun N-Terminal Kinase,c-jun Amino-Terminal Kinase,c-jun N-Terminal Kinase,jun-NH2-Terminal Kinase,jun-NH2-Terminal Kinases,Amino-Terminal Kinase, c-jun,JNK Mitogen Activated Protein Kinases,Kinase, jun N-Terminal,N-Terminal Kinase, c-jun,N-Terminal Kinase, jun,c jun Amino Terminal Kinase,c jun N Terminal Kinase,jun N Terminal Kinase,jun NH2 Terminal Kinase,jun NH2 Terminal Kinases

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