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Updated: Jul 6, 2026
09:59
Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein
Published on: March 9, 2015
Nonsteroidal anti-inflammatory drugs upregulate function of wild-type and mutant CFTR
1Research Building S104, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N3M5, Canada.
The European Respiratory Journal
|April 4, 2008
Summary
Ibuprofen, a nonsteroidal anti-inflammatory drug, can improve cystic fibrosis (CF) symptoms. This study reveals ibuprofen enhances CFTR function at low cAMP levels, offering new therapeutic insights for CFTR-related diseases.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Cystic Fibrosis (CF) is a genetic disorder caused by mutations in the CFTR gene.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen show clinical benefits in CF patients.
- Ibuprofen paradoxically inhibits ligand-stimulated CFTR activity in previous studies.
Purpose of the Study:
- To investigate the differential effects of ibuprofen on CFTR function under varying conditions.
- To explore ibuprofen's impact on wild-type and DeltaF580CFTR variants.
- To elucidate the role of cAMP levels in modulating ibuprofen's effect on CFTR.
Main Methods:
- Utilized patch-clamp recordings in human airway epithelial cell lines (IB3-8-3-7 with wild-type CFTR and IB3-1 with DeltaF580CFTR).
- Administered ibuprofen extracellularly and intracellularly.
- Manipulated intracellular cyclic adenosine monophosphate (cAMP) concentrations.
Main Results:
- Extracellular ibuprofen inhibited wild-type CFTR at high cAMP but enhanced it at low cAMP.
- Intracellular ibuprofen application abolished the enhancing effect.
- Ibuprofen enhanced DeltaF580CFTR-mediated conductance at endogenous cAMP levels in myoinositol-treated cells.
Conclusions:
- NSAIDs like ibuprofen can modulate CFTR function in a cAMP-dependent manner.
- Ibuprofen enhances both wild-type and DeltaF580CFTR activity at endogenous cAMP levels in airway epithelial cells.
- Findings suggest potential therapeutic applications of ibuprofen in CF treatment by targeting CFTR function.
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