Ibuprofen inhibits cystic fibrosis transmembrane conductance regulator-mediated Cl- secretion

J Clin Invest. 1998 Aug 15;102(4):679-87. doi: 10.1172/JCI2614.


We evaluated the acute effects of ibuprofen and salicylic acid on cAMP-mediated Cl- secretion (Isc) in both colonic and airway epithelia. In T84 cells, ibuprofen inhibited the forskolin-dependent Isc in a concentration-dependent manner, having an apparent Ki of 142 microM. Salicylic acid inhibited Isc with an apparent Ki of 646 microM. We determined whether ibuprofen would also inhibit the forskolin-stimulated Isc in primary cultures of mouse trachea epithelia (MTE) and human bronchial epithelia (HBE). Similar to our results in T84 cells, ibuprofen (500 microM) inhibited the forskolin-induced Isc in MTEs and HBEs by 59+/-4% (n = 11) and 39+/-6% (n = 8), respectively. Nystatin was employed to selectively permeabilize the basolateral or apical membrane to determine the effect of ibuprofen on apical Cl- (ICl) and basolateral K+ (IK) currents after stimulation by forskolin. After forskolin stimulation, ibuprofen (500 microM) reduced both the ICl and IK; reducing ICl and IK by 60 and 15%, respectively. To determine whether this inhibition of ICl was due to the inhibition of CFTR, the effects of ibuprofen and salicylic acid on CFTR Cl- channels in excised, inside-out patches from L-cells were evaluated. Ibuprofen (300 microM) reduced CFTR Cl- current by 60+/-16% and this was explained by a short-lived block (approximately 1.2 ms) which causes an apparent reduction in single channel amplitude from 1.07+/-0.04 pA to 0.59+/-0.04 pA (n = 3). Similarly, salicylic acid (3 mM) reduced CFTR Cl- current by 50+/-8% with an apparent reduction in single channel amplitude from 1.08+/-0.03 pA to 0.48+/-0.06 pA (n = 4). Based on these results, we conclude that the NSAIDs ibuprofen and salicylic acid inhibit cAMP-mediated Cl- secretion in human colonic and airway epithelia via a direct inhibition of CFTR Cl- channels as well as basolateral membrane K+ channels. This may reduce their efficacy in conjunction with other therapeutic strategies designed to increase CFTR expression and/or function in secretory epithelia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Biological Transport / drug effects
  • Bronchi / cytology
  • Bronchi / drug effects
  • Chlorides / metabolism*
  • Colon / cytology
  • Colon / drug effects
  • Cyclic AMP / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / drug effects*
  • Electric Conductivity
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Humans
  • Ibuprofen / pharmacology*
  • Mice
  • Potassium / metabolism
  • Salicylates / pharmacology
  • Salicylic Acid
  • Trachea / cytology
  • Trachea / drug effects


  • Anti-Inflammatory Agents, Non-Steroidal
  • CFTR protein, human
  • Chlorides
  • Salicylates
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cyclic AMP
  • Salicylic Acid
  • Potassium
  • Ibuprofen