title: Cystic fibrosis airway epithelium remodelling: involvement of inflammation.
abstract: Chronic inflammation is a hallmark of cystic fibrosis (CF) lung disease and airway epithelium damage and remodelling are important components of lung pathology progression in CF. Whether this remodelling is secondary to deleterious infectious and inflammatory mediators, or to alterations of CF human airway epithelial (HAE) cells, such as their hyper inflammatory phenotype or their basic cystic fibrosis transmembrane conductance regulator (CFTR) default, remains debated. In this study, we evaluated the involvement of alterations of CF HAE cells in airway epithelium remodelling. HAE cells from non-CF and CF patients were cultured in an air-liquid interface, with and without inflammatory stimulation, along the regeneration process, and the remodelling of the reconstituted epithelium was analysed. We confirmed that CF HAE cells showed a hyperinflammatory phenotype which was lost with time. In comparison to non-CF epithelium, CF epithelium regeneration in the absence of exogenous inflammation was higher and exhibited basal cell hyperplasia. This remodelling was mimicked by inflammatory stimulation of non-CF cells and was absent when CF HAE cells were no longer hyperinflamed. Moreover, the number of goblet cells was similar in non-CF and CF cultures and increased equally under inflammatory stimulation. Finally, whatever the inflammatory environment, CF cultures showed a delay in ciliated cell differentiation. In conclusion, alterations of CF HAE cells partly regulate airway epithelium remodelling following injury and regeneration. This remodelling, together with goblet cell hyperplasia induced by exogenous inflammation and alteration of ciliated cell differentiation, may worsen mucociliary clearance impairment, leading to injury.
authors.affiliation: INSERM UMR-S 903, SFR CAP-SANTE (FED 4231), University of Reims Champagne-Ardenne, Reims, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Adam
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Roux-Delrieu
authors.forename: Emilie
authors.initials: E
authors.lastname: Luczka
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bonnomet
authors.forename: Julien
authors.initials: J
authors.lastname: Lesage
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Mérol
authors.forename: Myriam
authors.initials: M
authors.lastname: Polette
authors.forename: Michel
authors.initials: M
authors.lastname: Abély
authors.forename: Christelle
authors.initials: C
authors.lastname: Coraux
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056151:Airway Remodeling / Q000502:physiology*; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000473:pathology* / Q000503:physiopathology; D016207:Cytokines / Q000494:pharmacology; D020397:Goblet Cells / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000473:pathology* / Q000503:physiopathology; D008875:Middle Aged; D010641:Phenotype; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: airway epithelium remodelling; airway inflammation; cystic fibrosis; regeneration