title: IL-17A induces Pendrin expression and chloride-bicarbonate exchange in human bronchial epithelial cells.
abstract: The epithelium plays an active role in the response to inhaled pathogens in part by responding to signals from the immune system. Epithelial responses may include changes in chemokine expression, increased mucin production and antimicrobial peptide secretion, and changes in ion transport. We previously demonstrated that interleukin-17A (IL-17A), which is critical for lung host defense against extracellular bacteria, significantly raised airway surface pH in vitro, a finding that is common to a number of inflammatory diseases. Using microarray analysis of normal human bronchial epithelial (HBE) cells treated with IL-17A, we identified the electroneutral chloride-bicarbonate exchanger Pendrin (SLC26A4) as a potential mediator of this effect. These data were verified by real-time, quantitative PCR that demonstrated a time-dependent increase in Pendrin mRNA expression in HBE cells treated with IL-17A up to 48 h. Using immunoblotting and immunofluorescence, we confirmed that Pendrin protein expression is increased in IL-17 treated HBE cells and that it is primarily localized to the mucosal surface of the cells. Functional studies using live-cell fluorescence to measure intracellular pH demonstrated that IL-17A induced chloride-bicarbonate exchange in HBE cells that was not present in the absence of IL-17A. Furthermore, HBE cells treated with short interfering RNA against Pendrin showed substantially reduced chloride-bicarbonate exchange. These data suggest that Pendrin is part of IL-17A-dependent epithelial changes and that Pendrin may therefore be a therapeutic target in IL-17A-dependent lung disease.
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Adams
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Valsamma
authors.initials: V
authors.lastname: Abraham
authors.affiliation: School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Spielman
authors.affiliation: Departments of Pediatrics and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Rubenstein
authors.affiliation: Department of Cell Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Conner
authors.affiliation: Department of Otorhinolaryngology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Noam A
authors.initials: NA
authors.lastname: Cohen
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: James L
authors.initials: JL
authors.lastname: Kreindler
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000076988:Sulfate Transporters
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D020381:Interleukin-17; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters