Bradykinin increases IL-8 generation in airway epithelial cells via COX-2-derived prostanoids.
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.
Rodgers
Helen C
HC
Division of Respiratory Medicine, City Hospital, Nottingham NG5 1PB, United Kingdom.
Pang
Linhua
L
Holland
Elaine
E
Corbett
Lisa
L
Range
Simon
S
Knox
Alan J
AJ
D016718:Arachidonic Acid / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis*; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016209:Interleukin-8; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001920:Bradykinin; D007213:Indomethacin