Submitted on August 22, 2007
Accepted on November 28, 2008
Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells
James L Kreindler1*, Carol A Bertrand2, Robert J. Lee3, Thomas Karasic4, Shean Aujla5, Joseph M Pilewski6, Raymond A. Frizzell7, and Jay K Kolls8
1 Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States
2 Cell Biology & Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
3 Physiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
4 Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States
5 Pediatrics , University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States
6 Division Pulm Allergy Crit Care Medicine, University Pittsburgh Sch Med, NW 628 MUH, Pittsburgh, Pennsylvania, 15213, United States; Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
7 Cell Biology & Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; Pediatrics , Children's Hospital of Pittsburgh , Pittsburgh, Pennsylvania, United States
8 Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
* To whom correspondence should be addressed. E-mail: kreindler{at}email.chop.edu.
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 hr 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 CFTR-dependent, mucosal chloride-dependent, partially sodium-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.
