title: Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. kreindler@email.chop.edu
authors.forename: James L
authors.initials: JL
authors.lastname: Kreindler
authors.forename: Carol A
authors.initials: CA
authors.lastname: Bertrand
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Thomas
authors.initials: T
authors.lastname: Karasic
authors.forename: Shean
authors.initials: S
authors.lastname: Aujla
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Pilewski
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Frizzell
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
mesh_terms: 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
chemical_list: 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