Effect of an agro-based compound (A-bC) on remodelling and regeneration of airway epithelium in cystic fibrosis
Abstract
The CF airway epithelium (AE) exhibits large areas of remodelling such as basal or goblet cell hyperplasia, ciliated cell absence or epithelial desquamation, therefore leading to impaired mucociliary clearance (MCC). We have previously demonstrated that the regeneration of CF AE leads to a remodelled epithelium, the role of CF cell inflammatory memory in basal cell hyperplasia and increased CF AE height, the involvement of lung tissue inflammation in goblet cell hyperplasia, and the inflammation-independent default of ciliated cell differentiation. The identification of therapies favouring MCC through an improvement of CF AE regeneration is therefore crucial for CF patients. In this perspective, we examined the influence of an agro-based compound (A-bC) obtained by bacterial fermentation of wheat, on the regeneration of the human CF AE.
Nasal epithelial cells from CF patients were cultured in air-liquid interface for 35 days in presence or not of A-bC and of Cytomix (TNF, IL1- and IFNcombo). Measurements on haematoxylin/eosin-stained sections of cultures showed that A-bC decreased the AE height, even in presence of chronic inflammation. Quantification of immunofluorescence-detected CK13-positive and MUC-5AC-positive cells indicated a decrease in basal and goblet cell number, respectively, in A-bC-treated cultures, with no influence of Cytomix on this effect. The number of -tubulin-positive ciliated cells was significantly increased in cultures exposed to A-bC, which also reduced the ELISA-measured IL-8 cell secretion.
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.