Aspirin and some other nonsteroidal anti-inflammatory drugs inhibit cysticfibrosis transmembrane conductance regulator protein gene expression in T-84 cells

CYSTIC fibrosis (CF) is caused by mutations in the CF gene, which encodes C F transmembrane conductance regulator protein (CFTR), a transmembrane prote in that acts as a cAMP-regulated chloride channel, The disease is character ized by inflammation but the relationship between inflammation, abnormal tr ansepithelial ion transport, and the clinical manifestations of CF are unce rtain. The present study was undertaken to determine whether three nonstero idal anti-inflammatory drugs (NSAIDs) (aspirin, ibuprofen, and indomethacin ) modulate CFTR gene expression in T-84 cells. Treatment with NSAIDs reduce d CFTR transcripts, and decreased cAMP-stimulated anion fluxes, an index of CFTR function. However, the two phenomena occurred at different concentrat ions of both drugs. The results indicate that NSAIDs can regulate both CFTR gene expression and the function of CFTR-related chloride transport, and s uggest that NSAIDs act via multiple transduction pathways.