The memory of airway epithelium damage in smokers and COPD patients
2021
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-, IL-6 and IL-1{beta}. 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.
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