Oxidative stress modulates the expression of genes involved in cell survival in ΔF508 cystic fibrosis airway epithelial cells

• Published in: Physiological genomics 2014-09, Vol.46 (17), p.634-646
• Main Authors: Voisin, Grégory, Bouvet, Guillaume F, Legendre, Pierre, Dagenais, André, Massé, Chantal, Berthiaume, Yves
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Apoptosis - genetics; Caspase 3 - metabolism; Caspase 7 - metabolism; Cell Line; Cell Survival - drug effects; Cell Survival - genetics; Cells, Cultured; Cystic Fibrosis - genetics; Cystic Fibrosis - pathology; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Down-Regulation - drug effects; Down-Regulation - genetics; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene Ontology; Humans; Inflammation - genetics; Lung - pathology; Naphthoquinones - pharmacology; Oxidative Stress - drug effects; Oxidative Stress - genetics; Reproducibility of Results; RNA, Messenger - genetics; RNA, Messenger - metabolism; Up-Regulation - drug effects; Up-Regulation - genetics
• ISSN: 1094-8341; 1531-2267
• DOI: 10.1152/physiolgenomics.00003.2014

Although cystic fibrosis (CF) pathophysiology is explained by a defect in CF transmembrane conductance regulator (CFTR) protein, the broad spectrum of disease severity is the consequence of environmental and genetic factors. Among them, oxidative stress has been demonstrated to play an important role in the evolution of this disease, with susceptibility to oxidative damage, decline of pulmonary function, and impaired lung antioxidant defense. Although oxidative stress has been implicated in the regulation of inflammation, its molecular outcomes in CF cells remain to be evaluated. To address the question, we compared the gene expression profile in NuLi-1 cells with wild-type CFTR and CuFi-1 cells homozygous for ΔF508 mutation cultured at air-liquid interface. We analyzed the transcriptomic response of these cell lines with microarray technology, under basal culture conditions and after 24 h oxidative stress induced by 15 μM 2,3-dimethoxy-1,4-naphtoquinone. In the absence of oxidative conditions, CuFi-1 gene profiling showed typical dysregulated inflammatory responses compared with NuLi-1. In the presence of oxidative conditions, the transcriptome of CuFi-1 cells reflected apoptotic transcript modulation. These results were confirmed in the CFBE41o- and corrCFBE41o- cell lines as well as in primary culture of human CF airway epithelial cells. Altogether, our data point to the influence of oxidative stress on cell survival functions in CF and identify several genes that could be implicated in the inflammation response observed in CF patients.