COPD-related epithelial inflammation drives EMT in primary epithelial ALI-cultures
(2018) ERS International Congress 2018 abstracts — Location: Paris
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- Airway inflammation is a constant feature in chronic obstructive pulmonary disease (COPD) but its role in driving abnormal broncho-epithelial phenotype remains unclear. We aimed to assess the contribution of epithelial inflammation to functional and structural changes of the airway epithelium (AE), including epithelial-to-mesenchymal transition (EMT). Methods: AE was reconstituted in air-liquid interface (ALI) cultures of human primary broncho-epithelial cells from COPD (n=12) versus control (n=12) subjects, recapitulating the abnormal phenotype in situ. The AE was treated by a cytokine mix (IL-1β, IL-6, TNF-α, 5ng/ml) up to 5 weeks, before assessing functional (transepithelial electric resistance (TER)), inflammatory (IL-8/CXCL-8 and IL-1α production), and differentiation features (polymeric immunoglobulin receptor (pIgR), secretory component (SC)), including EMT (fibronectin, vimentin). Results: Inflammatory conditioning (as compared to control) induced decreases in TER (2,787±280 vs 852±75 Ω/cm², mean±SEM of 24 experiments at 4wks, p<0.0001), SC production (6,324±881 vs 3,069±637 ng/ml, p<0.01) and pIgR expression. It also increased IL-8/CXCL-8 and IL-1α production (749±81 vs 137±15 ng/ml, p<0.0001 and 8.6±3.51 vs 1.23±1.23 pg/ml, p<0.05, respectively) as well as vimentin expression and fibronectin release (111.3±23.21 vs 6.51±2.03 ng/ml, p<0.01), the latter response being enhanced in COPD vs controls (+123±39 vs +19.6±10 ng/ml, p<0.05). Conclusions: These data show that (a) inflammation impairs both structure and function of the AE, and (b) COPD AE is more prone to inflammation-induced EMT than control AE, which could contribute to the persistence of epithelial dysfunction after smoking cessation.
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Carlier, F., Detry, B., Sibille, Y., & Pilette, C. (2018). COPD-related epithelial inflammation drives EMT in primary epithelial ALI-cultures. European Respiratory Journal. Supplement, 52(PA4239), PA4239. https://doi.org/10.1183/13993003.congress-2018.pa4239 (Original work published 2018)