Thiocyanate transport in resting and IL-4-stimulated human bronchial epithelial cells: Role of pendrin and anion channels

Nicoletta Pedemonte, Emanuela Caci, Elvira Sondo, Antonella Caputo, Kerry Rhoden, Ulrich Pfeffer, Michele Di Candia, Roberto Bandettini, Roberto Ravazzolo, Olga Zegarra-Moran, Luis J V Galietta

Research output: Contribution to journalArticle

Abstract

SCN- (thiocyanate) is an important physiological anion involved in innate defense of mucosal surfaces. SCN- is oxidized by H 2O2, a reaction catalyzed by lactoperoxidase, to produce OSCN- (hypothiocyanite), a molecule with antimicrobial activity. Given the importance of the availability of SCN- in the airway surface fluid, we studied transepithelial SCN- transport in Ore human bronchial epithelium. We found evidence for at least three mechanisms for basolateral to apical SCN- flux. cAMP and Ca2+ regulatory pathways controlled SCN- transport through cystic fibrosis transmembrane conductance regulator and Ca2+-activated Cl- channels, respectively, the latter mechanism being significantly increased by treatment with IL-4. Stimulation with EL-4 also indnced the strong upregulation of an electroneulral SCN-/Cl- exchange. Global gene expression analysis with microarrays and functional studies indicated pendrin (SLC26A4) as the protein responsible for this SCN- transport. Measurements of H2O2 production at the apical surface of bronchial cells indicated that the extent of SCN- transport is important to modulate the conversion of this oxidant molecule by the lactoperoxidase system. Our studies indicate that the human bronchial epithelium expresses various SCN- transport mechanisms under resting and stimulated conditions. Defects in SCN- transport in the airways may be responsible for susceptibility to infections and/or decreased ability to scavenge oxidants.

Original languageEnglish
Pages (from-to)5144-5153
Number of pages10
JournalJournal of Immunology
Volume178
Issue number8
Publication statusPublished - Apr 15 2007

ASJC Scopus subject areas

  • Immunology

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    Pedemonte, N., Caci, E., Sondo, E., Caputo, A., Rhoden, K., Pfeffer, U., Di Candia, M., Bandettini, R., Ravazzolo, R., Zegarra-Moran, O., & Galietta, L. J. V. (2007). Thiocyanate transport in resting and IL-4-stimulated human bronchial epithelial cells: Role of pendrin and anion channels. Journal of Immunology, 178(8), 5144-5153.