Bradykinin increases IL-8 generation in airway epithelial cells via COX-2-derived prostanoids

Am J Physiol Lung Cell Mol Physiol. 2002 Sep;283(3):L612-8. doi: 10.1152/ajplung.00483.2001.


Interleukin (IL)-8, the C-X-C chemokine, is a potent neutrophil chemoattractant that has been implicated in a number of inflammatory airway diseases such as cystic fibrosis. Here we tested the hypothesis that bradykinin, an inflammatory mediator and chloride secretagogue, would increase IL-8 generation in airway epithelial cells through autocrine generation of endogenous prostanoids. Bradykinin increased IL-8 generation in both a non-cystic fibrosis (A549) and cystic fibrosis epithelial cell line (CFTE29) that was inhibited by the nonselective cyclooxygenase (COX) inhibitor indomethacin and the COX-2 selective inhibitor NS-398. COX-2 was the only isoform of COX expressed in both cell lines. Furthermore, the COX substrate arachidonic acid and exogenous prostaglandin E(2) both increased IL-8 release in A549 cells. These results suggest that bradykinin may contribute to neutrophilic inflammation in the airway by generation of IL-8 from airway epithelial cells. The dependence of this response on endogenous production of prostanoids by COX-2 suggests that selective COX-2 inhibitors may have a role in the treatment of airway diseases characterized by neutrophilic inflammation such as cystic fibrosis or chronic obstructive pulmonary disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acid / pharmacology
  • Bradykinin / pharmacology*
  • Cell Line
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Cystic Fibrosis / metabolism
  • Dinoprostone / metabolism
  • Epithelial Cells / metabolism
  • Humans
  • Indomethacin / pharmacology
  • Interleukin-8 / biosynthesis*
  • Isoenzymes / metabolism*
  • Membrane Proteins
  • Nitrobenzenes / pharmacology
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Prostaglandins / metabolism*
  • Sulfonamides / pharmacology
  • Trachea / metabolism*


  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Interleukin-8
  • Isoenzymes
  • Membrane Proteins
  • Nitrobenzenes
  • Prostaglandins
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Arachidonic Acid
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Bradykinin
  • Indomethacin