Inflammatory Cytokines IL‐13 or IL‐17/TNFα Do Not Alter the Low Paracellular Bicarbonate Permeability of Cystic Fibrosis Airway Epithelia

Abstract

The airway‐surface liquid, the thin aqueous layer on the apical side of airway epithelia, maintains a pH that is more acidic than the serosal pH. For human large airways, this acidic pH is the balance of HCO3− secretion by the cystic fibrosis transmembrane conductance regulator (CFTR) and H+ secretion by the H+/K+ pump ATP12A, both transcellular mechanisms. Newborn humans with cystic fibrosis (CF) have an acidic airway‐surface liquid pH compared to non‐CF newborns. With time, the pH difference between CF and non‐CF individuals disappears. However, adult CF epithelia cultured at the air‐liquid interface are more acidic than non‐CF epithelia. We hypothesized that CF‐related inflammation in vivo is responsible for the age‐dependent airway alkalinization. Here, we tested the hypothesis that cytokines increase paracellular movement of HCO3− into the airway‐surface liquid. Dilution potentials observed for cultured CF airway indicate that paracellular transport favored cations (PCl/PNa = 0.7). The paracellular conductance and selectivity were unaffected by changing the pH from 7.4 to 6.0. HCO3− was less permeable than Cl− through the paracellular pathway (PHCO3/PNa = 0.35). Treating cultures with cytokines (IL‐13 or IL‐17 and TNFa), which increase the airway‐surface liquid pH, did not affect paracellular PHCO3/PNa. These data suggest that differences in transcellular pH transport are responsible for cytokine‐mediated ASL pH changes. Similar transcellular mechanisms may cause the longitudinal ASL pH changes observed for CF patients.Support or Funding InformationMJW is an Investigator of the Howard Hughes Medical InstituteCystic Fibrosis Foundation Research Development ProgramNIH HL091842This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.