Abstract
Background Chronic obstructive pulmonary disease (COPD) is a devastating lung disease, representing the third cause of mortality worldwide. In COPD, the bronchial epithelium displays several structural and functional abnormalities involving barrier integrity, polarity, cell differentiation and epithelial-to-mesenchymal transition, as well as inflammation. Although COPD is currently considered as an irreversible disease, the (ir)reversible nature of those changes ex vivo remains poorly known.
Methods The persistence of COPD epithelial features was assessed in very long-term (10 weeks) primary cultures of air/liquid interface (ALI)-reconstituted airway epithelium from non-smoker controls, smoker controls, and COPD patients. The role of inflammation in promoting this phenotype was also explored by stimulating ALI cultures with a cytokine mix of TNF-α, IL-6 and IL-1β.
Results Almost all epithelial defects (barrier dysfunction, impaired polarity, lineage abnormalities) observed in smokers and COPD persisted in vitro up to week 10, except IL-8 release and epithelial-to-mesenchymal transition which declined over time. Cytokine treatment induced COPD-like changes and was able to reactivate epithelial-to-mesenchymal transition in COPD cells.
Conclusions The airway epithelium from smokers and COPD patients displays a memory of its native state and previous injuries by cigarette smoking, which is multidimensional and sustained for years, therefore probably residing in basal stem cells.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Sources of support. This work was supported by the Fondation Mont-Godinne, Belgium, grant to FC (N°FMG-2015-BC01, FMG-2016-BC01, and FMG-2017-BC01) by the Fonds National de Recherche Scientifique (FNRS), Belgium, grant to FC (N°1.L505.18) and to CP (N°1.R016.16 and 1.R016.18). Funders were not involved in study design, data collection, data analysis, interpretation, or writing of the manuscript.
Competing interests. The authors have nothing to disclose.