RT Journal Article
SR Electronic
T1 The memory of airway epithelium damage in smokers and COPD patients
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.21.439437
DO 10.1101/2021.04.21.439437
A1 François M. Carlier
A1 Bruno Detry
A1 Marylène Lecocq
A1 Amandine M. Collin
A1 Stijn E. Verleden
A1 Claudia M. Stanciu-Pop
A1 Wim Janssens
A1 Jérôme Ambroise
A1 Bart M. Vanaudenaerde
A1 Sophie T. Gohy
A1 Charles Pilette
YR 2021
UL http://biorxiv.org/content/early/2021/04/22/2021.04.21.439437.abstract
AB 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 StatementThe authors have declared no competing interest.