1. Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells.
- Author
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Kreindler, James L., Bertrand, Carol A., Lee, Robert J., Karasic, Thomas, Aujla, Shean, Pilewski, Joseph M., Frizzell, Raymond A., and Kolls, Jay K.
- Subjects
PEPTIDES ,INTERLEUKINS ,GENETIC disorders ,CYSTIC fibrosis ,CELLS ,CELLULAR immunity ,T 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. [ABSTRACT FROM AUTHOR]- Published
- 2009
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