Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epithelium

• Published in: Respiratory research 2017-05, Vol.18 (1), p.82-82, Article 82
• Main Authors: Murray, Lynne A, Dunmore, Rebecca, Camelo, Ana, Da Silva, Carla A, Gustavsson, Malin J, Habiel, David M, Hackett, Tillie L, Hogaboam, Cory M, Sleeman, Matthew A, Knight, Darryl A
• Format: Article
• Language: English
• Subjects: Aberration; Acute effects; Airway management; Animals; Antigens; Apoptosis; Apoptosis - drug effects; Cancer; Cell activation; Cell growth; Cell proliferation; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarettes; Cytokines; Epithelial cells; Epithelial-Mesenchymal Transition - drug effects; Epithelium; Experiments; Exposure; Fibrosis; Fragility; Gene expression; Genotype & phenotype; Health risks; Humans; Hyperplasia; In vitro methods and tests; Inflammation; Kinases; Lung cancer; Lung diseases; Mesenchyme; Mice; Mice, Inbred C57BL; Mimicry; Obstructive lung disease; Poly I:C; Polyinosinic:polycytidylic acid; Pulmonary Disease, Chronic Obstructive - chemically induced; Pulmonary Disease, Chronic Obstructive - pathology; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - pathology; Pulmonary Fibrosis - physiopathology; Remodelling; Respiratory Mucosa - drug effects; Respiratory Mucosa - pathology; Respiratory Mucosa - physiopathology; Respiratory tract; Risk analysis; Risk factors; Smoke; Smoke - adverse effects; Smoking; TGFβ1; Tobacco Products - poisoning; Viruses
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-017-0565-2

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. 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. 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.