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This Article Full Text Full Text (PDF) All Versions of this Article: 296/2/L257    most recent 00344.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kreindler, J. L. Articles by Kolls, J. K. Search for Related Content PubMed PubMed Citation Articles by Kreindler, J. L. Articles by Kolls, J. K.

Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells

¹Division of Pulmonary Medicine, Department of Pediatrics and ⁵Department of Physiology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia; ²Division of Pulmonary Medicine, Allergy, and Immunology, Department of Pediatrics, Children's Hospital of Pittsburgh, ³Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and ⁴Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Submitted 22 August 2007 ; accepted in final form 28 November 2008

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.

cystic fibrosis; airway surface liquid; pH; cystic fibrosis transmembrane conductance regulator; anion exchange