Document Detail

Ibuprofen rescues mutant cystic fibrosis transmembrane conductance regulator trafficking.
MedLine Citation:
PMID:  24974227     Owner:  NLM     Status:  Publisher    
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
Graeme W Carlile; Renaud Robert; Julie Goepp; Elizabeth Matthes; Jie Liao; Bart Kus; Sean D Macknight; Daniela Rotin; John W Hanrahan; David Y Thomas
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-25
Journal Detail:
Title:  Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society     Volume:  -     ISSN:  1873-5010     ISO Abbreviation:  J. Cyst. Fibros.     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-6-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128966     Medline TA:  J Cyst Fibros     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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