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

卷:18

Darryl A. Knight¹  Tillie L Hackett¹  David M. Habiel²  Cory M. Hogaboam²  Malin J. Gustavsson³  Carla A. Da Silva³  Lynne A. Murray⁴  Ana Camelo⁴  Matthew A. Sleeman⁴  Rebecca Dunmore⁴ 

[1] Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia;

[2] Department of Medicine, Cedars-Sinai Medical Center;

[3] Respiratory, Inflammation and Autoimmunity innovative Medicines Unit, AstraZeneca R&D;

[4] Respiratory, Inflammation and Autoimmunity, MedImmune Ltd;

关键词: TGFβ1;    Poly I:C;    Remodelling;    Apoptosis;   

DOI  :  10.1186/s12931-017-0565-2

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown