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Abstract
The bronchial epithelium in chronic obstructive pulmonary disease (COPD) displays hyperplastic goblet- and basal cells, decreased ciliated cells and epithelial-to-mesenchymal transition (EMT) features. Whether these features are irreversible is incompletely understood. We aimed to delineate the plasticity of the abnormal broncho-epithelial phenotype in COPD. Methods: The airway epithelium (AE) reconstituted in air-liquid interface (ALI) cultures of human primary broncho-epithelial cells from COPD (vs controls), recapitulating the abnormal phenotype observed in situ, was assessed up to 10 weeks for functional (transepithelial electric resistance (TER)), inflammatory (IL-8/CXCL-8 and IL-1α production) and differentiation features including EMT (fibronectin, vimentin). Results: COPD AE show a persistent decrease in TER versus controls (p<0.0001). In contrast, the initial increases of vimentin and fibronectin production in COPD (fibronectin at 1 week, 62.69±16.2 versus 7.81±1.79 ng/ml in controls, p<0.01) disappeared at 4 weeks onwards, while IL-8/CXCL-8 overproduction in COPD disappeared at 7 weeks onwards (Figure 1). Conclusions: These data suggest that certain structural changes of the COPD epithelium - such as reduced barrier integrity - are fixed whereas others – such as EMT and inflammatory features – are reversible in vitro. Further studies should delineate the respective underlying mechanisms.
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Carlier, F., Detry, B., Sibille, Y., & Pilette, C. (2018). COPD epithelial phenotype shows partial reversibility in long-term primary epithelial ALI-cultures. European Respiratory Journal. Supplement, 52(OA502), OA205. https://doi.org/10.1183/13993003.congress-2018.oa502 (Original work published 2018)