Fig. 4.

Non-CFTR mechanism(s) mediate TNFα+IL-17-induced airway surface liquid (ASL) alkalinization and operate in tandem with CFTR. Human airway epithelia were treated with TNFα+IL-17 for 24 h, and pH of ASL (pH_ASL) was measured with SNARF-1-dextran in the presence of ${\text{HCO}}_3^{-}$/CO₂. pH_ASL values were converted to [H⁺]_ASL, and net alkalinization was calculated as the difference (Δ[H⁺]_ASL) between control and TNFα+IL-17-treated epithelia. A: TNFα+IL-17-induced alkalinization in non-cystic fibrosis (CF) vs. CF epithelia (n = 12 different donors for non-CF and 11 different donors for CF group). B: TNFα+IL-17-induced alkalinization in CF donors carrying at least one F508-CFTR allele. Epithelia were treated with either vehicle (DMSO) or the recently approved triple combination of CFTR correctors (3 μM VX-445, 18 μM VX-661, 1 μM VX-770) for 48 h, with the addition of cytokines for the last 24 h (n = 6). CF epithelia in A and B were from different donors and were studied at different times. Bars indicate means ± SD. Groups were compared with unpaired (A) or paired (B) Student’s t test. **P < 0.01.