Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells.
The innate immune functions of human airways include mucociliary clearance and antimicrobial peptide activity. Both functions may be affected by changes in epithelial ion transport. Interleukin-17A (IL-17A), which has a receptor at the basolateral membrane of airway epithelia, is a T cell cytokine that has been shown to increase mucus secretion and antimicrobial peptide production by human bronchial epithelial (HBE) cells. Furthermore, IL-17A levels are increased in sputum from patients during pulmonary exacerbations of cystic fibrosis. Therefore, we investigated the effects of IL-17A on basal, amiloride-sensitive, and forskolin-stimulated ion transport in mature, well-differentiated HBE cells. Exposure of HBE monolayers to IL-17A for 48 h induced a novel forskolin-stimulated bicarbonate secretion in addition to forskolin-stimulated chloride secretion and resulted in alkalinization of liquid on the mucosal surface of polarized cells. IL-17A-induced bicarbonate secretion was cystic fibrosis transmembrane conductance regulator (CFTR)-dependent, mucosal chloride-dependent, partially Na(+)-dependent, and sensitive to serosal, but not mucosal, stilbene inhibition. These data suggest that IL-17A modulates epithelial bicarbonate secretion and implicate a mechanism by which airway surface liquid pH changes may be abnormal in cystic fibrosis.
Kreindler
James L
JL
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. kreindler@email.chop.edu
Bertrand
Carol A
CA
Lee
Robert J
RJ
Karasic
Thomas
T
Aujla
Shean
S
Pilewski
Joseph M
JM
Frizzell
Raymond A
RA
Kolls
Jay K
JK
D000584:Amiloride / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D026941:Sodium Channel Blockers / Q000494:pharmacology
D001639:Bicarbonates; C505032:CFTR protein, human; D018118:Chloride Channels; D002712:Chlorides; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D020381:Interleukin-17; D026941:Sodium Channel Blockers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D000584:Amiloride