TY - JOUR T1 - Nonsteroidal anti-inflammatory drugs upregulate function of wild-type and mutant CFTR JF - European Respiratory Journal JO - Eur Respir J SP - 334 LP - 343 DO - 10.1183/09031936.00168007 VL - 32 IS - 2 AU - J. Li AU - Y-Y. Xiang AU - L. Ye AU - L-C. Tsui AU - J. F. MacDonald AU - J. Hu AU - W-Y. Lu Y1 - 2008/08/01 UR - http://erj.ersjournals.com/content/32/2/334.abstract N2 - Small-scale clinical trials show that treatment of cystic fibrosis (CF) patients with ibuprofen, a nonsteroidal anti-inflammatory drug, improves the symptoms of CF and slows down the decline of lung function. Paradoxically, ibuprofen inhibits ligand-stimulated CF transmembrance conductance regulator (CFTR) activity. The aim of the present study was to investigate the effects of ibuprofen on CFTR function under different conditions. Patch-clamp recordings were performed in two lines of human airway epithelial cells: IB3-8-3-7 cells, which express wild-type CFTR; and IB3-1 cells, which express the variant CFTR with deletion of phenylalanine 580 (ΔF580CFTR). Addition of ibuprofen to the extracellular solution caused a rapid inhibition of CFTR activity in IB3-8-3-7 cells in the presence of a high intracellular concentration of cAMP, whereas ibuprofen enhanced the CFTR conductance at low levels of cAMP. Introducing ibuprofen into the interior of cells occluded the enhancing effect of ibuprofen. Notably, the variant CFTR-mediated conductance was detected in IB3-1 cells treated with myoinositol and was enhanced by ibuprofen at endogenous levels of cAMP. In summary, nonsteroidal anti-inflammatory drugs increase the function of both wild-type cystic fibrosis transmembrane conductance regulator and the phenylalanine 580 deletion in cultured human airway epithelial cells at endogenous levels of cAMP. ER -