The Effect of Sodium Bicarbonate, a Beneficial Adjuvant Molecule in Cystic Fibrosis, on Bronchial Epithelial Cells Expressing a Wild-Type or Mutant CFTR Channel

International Journal of Molecular Sciences

Fabien Gosselet¹  Ákos Zsembery²  Pongsiri Jaikumpun²  Gabriella Fűr³  Lóránd Kiss³  Zoltán Rakonczay, Jr.³  Hajnalka Szabó⁴  Lilla Barna⁵  András Harazin⁵  Gaszton Vizsnyiczai⁵  Mária A. Deli⁵  Ilona Gróf⁵  Alexandra Bocsik⁵  Ana Raquel Santa-Maria⁵  Rita Ambrus⁶  Piroska Szabó-Révész⁶ 

[1] Blood-Brain Barrier Laboratory, UR 2465, Artois University, F-62300 Lens, France;Department of Oral Biology, Semmelweis University, H-1089 Budapest, Hungary;Department of Pathophysiology, University of Szeged, H-6725 Szeged, Hungary;Department of Pediatrics, Fejér County Szent György University Teaching Hospital, H-8000 Székesfehérvár, Hungary;Institute of Biophysics, Biological Research Centre, H-6726 Szeged, Hungary;Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, H-6720 Szeged, Hungary;

关键词: bronchial epithelial cells;    CFTR channel;    cystic fibrosis;    cytokine;    impedance kinetics;    permeability;   

DOI  :  10.3390/ijms21114024

来源: DOAJ

【 摘 要 】

Clinical and experimental results with inhaled sodium bicarbonate as an adjuvant therapy in cystic fibrosis (CF) are promising due to its mucolytic and bacteriostatic properties, but its direct effect has not been studied on respiratory epithelial cells. Our aim was to establish and characterize co-culture models of human CF bronchial epithelial (CFBE) cell lines expressing a wild-type (WT) or mutant (deltaF508) CF transmembrane conductance regulator (CFTR) channel with human vascular endothelial cells and investigate the effects of bicarbonate. Vascular endothelial cells induced better barrier properties in CFBE cells as reflected by the higher resistance and lower permeability values. Activation of CFTR by cAMP decreased the electrical resistance in WT but not in mutant CFBE cell layers confirming the presence and absence of functional channels, respectively. Sodium bicarbonate (100 mM) was well-tolerated by CFBE cells: it slightly reduced the impedance of WT but not that of the mutant CFBE cells. Sodium bicarbonate significantly decreased the more-alkaline intracellular pH of the mutant CFBE cells, while the barrier properties of the models were only minimally changed. These observations indicate that sodium bicarbonate is beneficial to deltaF508-CFTR expressing CFBE cells. Thus, sodium bicarbonate may have a direct therapeutic effect on the bronchial epithelium.

【 授权许可】

Unknown