Article: Nonsteroidal anti-inflammatory drugs upregulate function of wild-type and mutant CFTR

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Publisher Website: 10.1183/09031936.00168007
Scopus: eid_2-s2.0-55149090254
PMID: 18385167
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Title	Nonsteroidal anti-inflammatory drugs upregulate function of wild-type and mutant CFTR
Authors	Li, J3 Xiang, YY3 Ye, L5 Tsui, LC2 5 MacDonald, JF1 Hu, J3 5 Lu, WY1 3 4
Keywords	Adenylate cyclase Chloride channel Forskolin Lung epithelium Perforated-patch recording
Issue Date	2008
Publisher	European Respiratory Society. The Journal's web site is located at http://erj.ersjournals.com
Citation	European Respiratory Journal, 2008, v. 32 n. 2, p. 334-343 [How to Cite?] DOI: http://dx.doi.org/10.1183/09031936.00168007
Abstract	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. Copyright©ERS Journals Ltd 2008.
ISSN	0903-1936 2011 Impact Factor: 5.895 2011 SCImago Journal Rankings: 0.466
DOI	http://dx.doi.org/10.1183/09031936.00168007
ISI Accession Number ID	WOS:000258417000014
References	References in Scopus

DC Field	Value
dc.contributor.author	Li, J
dc.contributor.author	Xiang, YY
dc.contributor.author	Ye, L
dc.contributor.author	Tsui, LC
dc.contributor.author	MacDonald, JF
dc.contributor.author	Hu, J
dc.contributor.author	Lu, WY
dc.date.accessioned	2011-11-25T08:30:12Z
dc.date.available	2011-11-25T08:30:12Z
dc.date.issued	2008
dc.description.abstract	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. Copyright©ERS Journals Ltd 2008.
dc.description.nature	link_to_OA_fulltext
dc.identifier.citation	European Respiratory Journal, 2008, v. 32 n. 2, p. 334-343 [How to Cite?] DOI: http://dx.doi.org/10.1183/09031936.00168007
dc.identifier.doi	http://dx.doi.org/10.1183/09031936.00168007
dc.identifier.epage	343
dc.identifier.isi	WOS:000258417000014
dc.identifier.issn	0903-1936 2011 Impact Factor: 5.895 2011 SCImago Journal Rankings: 0.466
dc.identifier.issue	2
dc.identifier.openurl
dc.identifier.pmid	18385167
dc.identifier.scopus	eid_2-s2.0-55149090254
dc.identifier.spage	334
dc.identifier.uri	http://hdl.handle.net/10722/143454
dc.identifier.volume	32
dc.language	eng
dc.publisher	European Respiratory Society. The Journal's web site is located at http://erj.ersjournals.com
dc.publisher.place	Switzerland
dc.relation.ispartof	European Respiratory Journal
dc.relation.references	References in Scopus
dc.subject.mesh	Anti-Inflammatory Agents, Non-Steroidal - pharmacology
dc.subject.mesh	Cystic Fibrosis - metabolism
dc.subject.mesh	Cystic Fibrosis Transmembrane Conductance Regulator - genetics - metabolism
dc.subject.mesh	Lung - drug effects - microbiology - pathology
dc.subject.mesh	Mutation
dc.subject	Adenylate cyclase
dc.subject	Chloride channel
dc.subject	Forskolin
dc.subject	Lung epithelium
dc.subject	Perforated-patch recording
dc.title	Nonsteroidal anti-inflammatory drugs upregulate function of wild-type and mutant CFTR
dc.type	Article

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Author Affiliations

University of Toronto, Faculty of Medicine
The University of Hong Kong
University of Toronto
Sunnybrook Health Sciences Centre
Hospital for Sick Children, Toronto