Effect of an agro-based compound (A-bC) on regeneration of airway epithelium in Cystic Fibrosis (CF)

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The CF airway epithelium (AE) exhibits large areas of basal or goblet cell hyperplasia, ciliated cell absence or epithelial desquamation, leading to impaired mucociliary clearance (MCC). Lung tissue inflammation leads to goblet cell hyperplasia, CF AE cell inflammatory memory to basal cell hyperplasia and increased AE height, and ciliated cell defect is independent of inflammation. Identification of therapies favouring MCC through CF AE regeneration improvement is crucial for CF patients. We therefore examined the influence of an A-bC on human CF AE regeneration. Nasal epithelial cells from CF patients were cultured in air-liquid interface in presence or not of A-bC and of Cytomix (TNFα, IL1-β and IFNγcombo). Measurements on hematoxylin/eosin stained culture sections showed that A-bC decreased AE height, even in the presence of chronic inflammation. Quantification of CK13 and MUC-5AC-positive cells detected by immunofluorescence indicated a decrease in the number of basal and goblet cells, respectively, in cultures treated with A-bC, with no influence of Cytomix on this effect. The number of β-tubulin-positive ciliated cells increased significantly in cultures exposed to A-bC, which also reduced IL-8 cell secretion, as measured by ELISA. In conclusion, A-bC avoids the inflammation-related CF AE remodelling, probably through the modulation of cell inflammatory phenotype. Moreover, A-bC improves the ciliogenesis by a mechanism independent of its anti-inflammatory effect. These data allow us to propose A-bC as a pro-regenerative compound favouring key parameters for efficient MCC function in the CF AE. Supported by Vaincre La Mucoviscidose, Inserm and Friends of the AMH of Reims.

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