Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epithelium
Abstract Background Smoking and aberrant epithelial responses are risk factors for lung cancer as well as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. In these conditions, disease progression is associated with epithelial damage and fragility, airway remodelling and sub-e...
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doaj-40130925c55a4bc29eb4f09272bb4f312020-11-25T01:29:28ZengBMCRespiratory Research1465-993X2017-05-0118111210.1186/s12931-017-0565-2Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epitheliumLynne A. Murray0Rebecca Dunmore1Ana Camelo2Carla A. Da Silva3Malin J. Gustavsson4David M. Habiel5Tillie L Hackett6Cory M. Hogaboam7Matthew A. Sleeman8Darryl A. Knight9Respiratory, Inflammation and Autoimmunity, MedImmune LtdRespiratory, Inflammation and Autoimmunity, MedImmune LtdRespiratory, Inflammation and Autoimmunity, MedImmune LtdRespiratory, Inflammation and Autoimmunity innovative Medicines Unit, AstraZeneca R&DRespiratory, Inflammation and Autoimmunity innovative Medicines Unit, AstraZeneca R&DDepartment of Medicine, Cedars-Sinai Medical CenterDepartment of Anesthesiology, Pharmacology and Therapeutics, University of British ColumbiaDepartment of Medicine, Cedars-Sinai Medical CenterRespiratory, Inflammation and Autoimmunity, MedImmune LtdDepartment of Anesthesiology, Pharmacology and Therapeutics, University of British ColumbiaAbstract Background Smoking and aberrant epithelial responses are risk factors for lung cancer as well as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. In these conditions, disease progression is associated with epithelial damage and fragility, airway remodelling and sub-epithelial fibrosis. The aim of this study was to assess the acute effects of cigarette smoke on epithelial cell phenotype and pro-fibrotic responses in vitro and in vivo. Results Apoptosis was significantly greater in unstimulated cells from COPD patients compared to control, but proliferation and CXCL8 release were not different. Cigarette smoke dose-dependently induced apoptosis, proliferation and CXCL8 release with normal epithelial cells being more responsive than COPD patient derived cells. Cigarette smoke did not induce epithelial-mesenchymal transition. In vivo, cigarette smoke exposure promoted epithelial apoptosis and proliferation. Moreover, mimicking a virus-induced exacerbation by exposing to mice to poly I:C, exaggerated the inflammatory responses, whereas expression of remodelling genes was similar in both. Conclusions Collectively, these data indicate that cigarette smoke promotes epithelial cell activation and hyperplasia, but a secondary stimulus is required for the remodelling phenotype associated with COPD.http://link.springer.com/article/10.1186/s12931-017-0565-2TGFβ1Poly I:CRemodellingApoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lynne A. Murray Rebecca Dunmore Ana Camelo Carla A. Da Silva Malin J. Gustavsson David M. Habiel Tillie L Hackett Cory M. Hogaboam Matthew A. Sleeman Darryl A. Knight |
spellingShingle |
Lynne A. Murray Rebecca Dunmore Ana Camelo Carla A. Da Silva Malin J. Gustavsson David M. Habiel Tillie L Hackett Cory M. Hogaboam Matthew A. Sleeman Darryl A. Knight Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epithelium Respiratory Research TGFβ1 Poly I:C Remodelling Apoptosis |
author_facet |
Lynne A. Murray Rebecca Dunmore Ana Camelo Carla A. Da Silva Malin J. Gustavsson David M. Habiel Tillie L Hackett Cory M. Hogaboam Matthew A. Sleeman Darryl A. Knight |
author_sort |
Lynne A. Murray |
title |
Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epithelium |
title_short |
Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epithelium |
title_full |
Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epithelium |
title_fullStr |
Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epithelium |
title_full_unstemmed |
Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epithelium |
title_sort |
acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in copd epithelium |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-993X |
publishDate |
2017-05-01 |
description |
Abstract Background Smoking and aberrant epithelial responses are risk factors for lung cancer as well as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. In these conditions, disease progression is associated with epithelial damage and fragility, airway remodelling and sub-epithelial fibrosis. The aim of this study was to assess the acute effects of cigarette smoke on epithelial cell phenotype and pro-fibrotic responses in vitro and in vivo. Results Apoptosis was significantly greater in unstimulated cells from COPD patients compared to control, but proliferation and CXCL8 release were not different. Cigarette smoke dose-dependently induced apoptosis, proliferation and CXCL8 release with normal epithelial cells being more responsive than COPD patient derived cells. Cigarette smoke did not induce epithelial-mesenchymal transition. In vivo, cigarette smoke exposure promoted epithelial apoptosis and proliferation. Moreover, mimicking a virus-induced exacerbation by exposing to mice to poly I:C, exaggerated the inflammatory responses, whereas expression of remodelling genes was similar in both. Conclusions Collectively, these data indicate that cigarette smoke promotes epithelial cell activation and hyperplasia, but a secondary stimulus is required for the remodelling phenotype associated with COPD. |
topic |
TGFβ1 Poly I:C Remodelling Apoptosis |
url |
http://link.springer.com/article/10.1186/s12931-017-0565-2 |
work_keys_str_mv |
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