Referenced in: none

Automatically associated channels: Slo1

Title: Ibuprofen rescues mutant cystic fibrosis transmembrane conductance regulator trafficking.

Authors: Graeme W Carlile, Renaud Robert, Julie Goepp, Elizabeth Matthes, Jie Liao, Bart Kus, Sean D Macknight, Daniela Rotin, John W Hanrahan, David Y Thomas

Journal, date & volume: J. Cyst. Fibros., 2015 Jan , 14, 16-25

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24974227

Abstract
Small molecules as shown by VX809 can rescue the mislocalization of F508del-CFTR. The aim of this study was to identify correctors with a clinical history and their targets of action.CFTR correctors were screened using two F508del-CFTR expressing cell based HTS assays. Electrophysiological studies using CFBE41o(-) and HBE cells and in-vivo mouse assays confirmed CFTR rescue. The target of action was attained using pharmacological inhibitors and siRNA to specific genes.Ibuprofen was identified as a CFTR corrector. Ibuprofen treatment of polarized CFBE41o(-) monolayers increased the short-circuit current (Isc) response to stimulation. In vivo CF mice treatment with ibuprofen restored the CFTR trafficking. SiRNA knock down of cyclooxygenase expression caused partial F508del-CFTR correction.These studies show that ibuprofen is a CFTR corrector and that it causes correction by COX-1 inhibition. Hence ibuprofen may be suitable to be part of a future CF combination therapy.