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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40360-020-00451-0","type":"journal-article","created":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T09:03:13Z","timestamp":1604134993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Tiotropium\/Olodaterol treatment reduces cigarette smoke extract-induced cell death in BEAS-2B bronchial epithelial cells"],"prefix":"10.1186","volume":"21","author":[{"given":"Cheng-hsiung","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Rong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng-Hao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu-Hui","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woei-Horng","family":"Chai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Chiang","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9407-8578","authenticated-orcid":false,"given":"Ching-Hsiung","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,10,31]]},"reference":[{"issue":"13","key":"451_CR1","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1056\/NEJMra1900475","volume":"381","author":"A Agust\u00ed","year":"2019","unstructured":"Agust\u00ed A, Hogg JC. 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