The effect of sodium bicarbonate, a beneficial adjuvant molecule in cystic fibrosis, on bronchial epithelial cells expressing a wild-type or mutant CFTR channel

Ilona Gróf, Alexandra Bocsik, András Harazin, Ana Raquel Santa-Maria, Gaszton Vizsnyiczai, Lilla Barna, Lóránd Kiss, Gabriella Fűr, Zoltán Rakonczay, Rita Ambrus, Piroska Szabó-Révész, Fabien Gosselet, Pongsiri Jaikumpun, Hajnalka Szabó, Ákos Zsembery, Mária A. Deli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number4024
JournalInternational journal of molecular sciences
Volume21
Issue number11
DOIs
Publication statusPublished - Jun 1 2020

Keywords

  • Bronchial epithelial cells
  • CFTR channel
  • Cystic fibrosis
  • Cytokine
  • Impedance kinetics
  • Permeability
  • Sodium bicarbonate
  • Tight junctions
  • Transepithelial electric resistance

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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