WS2.6 Potassium channel currents induced by lipoxin stimulate airway epithelial repair

Abstract

In CF, the airway epithelium is frequently remodeled and has to rapidly regenerate its structure. Whether these alterations are related to infection and/or inflammation or to a dysregulated regeneration process remains to be elucidated. Previously, we showed in an aseptic xenograft model that CF epithelial regeneration is delayed and reconstitute a remodeled epithelium. The aim of the present study was to determine if CF airway epithelial regeneration is abnormal in absence of endogenous inflammation. CF and non-CF epithelial cells collected from aseptic nasal polyps were cultured at the air-liquid interface. Histology and cell proliferation were examined on culture sections after histological or immunological staining. Epithelial functionality was assessed in terms of electrical properties and bactericidal activity of epithelial secretions. In absence of endogenous inflammation, the CF epithelial regeneration is delayed. The regenerated epithelium is remodeled, exhibits basal cell hyperplasia and is significantly thicker compared to non-CF. However, a delay in cell proliferation, rather than hyperproliferation, is observed. Finally, the CF regenerated epithelium is not functional. We show here that in absence of exogenous infection and inflammation, the CF regenerated epithelium is a remodeled. This strongly suggests the involvement of the basic CFTR default in this phenomenon. To verify this hypothesis, we will examine the regeneration process of cells after treatment with CFTR correctors or CFTR-encoding lentiviral vectors to correct CF cells, as well as CFTR siRNAs to silence CFTR in non-CF cells. We thank Vaincre la Mucoviscidose, Region Champagne-Ardenne and INSERM.