Transepithelial ion transport is suppressed in hypoxic sinonasal epithelium

Academic Article

Abstract

  • Objectives/Hypothesis: Sinonasal respiratory epithelial mucociliary clearance is dependent on the transepithelial transport of ions such as Cl -. The objectives of the present study were to investigate the role of oxygen restriction in 1) Cl - transport across primary sinonasal epithelial monolayers, 2) expression of the apical Cl - channels cystic fibrosis transmembrane conductance regulator (CFTR) and transmembrane protein 16A (TMEM16A), and 3) the pathogenesis of chronic rhinosinusitis. Study Design: In vitro investigation. Methods: Murine nasal septal epithelial (MNSE), wild type, and human sinonasal epithelial (HSNE) cultures were incubated under hypoxic conditions (1% O 2, 5% CO 2). Cultures were mounted in Ussing chambers for ion transport measurements. CFTR and TMEM16A expression were measured using quantitative reverse-transcription polymerase chain reaction (RT-PCR). Results: The change in short-circuit current (ΔI SC in microamperes per square centimeter) attributable to CFTR (forskolin- stimulated) was significantly decreased due to a 12-hour hypoxia exposure in both MNSE (13.55 ± 0.46 vs. 19.23 ± 0.18) and HSNE (19.55 ± 0.56 vs. 25.49 ± 1.48 [control]; P <.05). TMEM16A (uridine triphosphate-stimulated transport) was inhibited by 48 hours of hypoxic exposure in MNSE (15.92 ± 2.87 vs. 51.44 ± 3.71 [control]; P <.05) and by 12 hours of hypoxic exposure in HSNE (16.75 ± 0.68 vs. 24.15 ± 1.35 [control]). Quantitative RT-PCR (reported as relative mRNA levels ± standard deviation) demonstrated significant reductions in both CFTR and TMEM16A mRNA expression in MNSE and HSNE owing to airway epithelial hypoxia. Conclusions: Sinonasal epithelial CFTR and TMEM16A-mediated Cl - transport and mRNA expression were robustly decreased in an oxygen-restricted environment. These findings indicate that persistent hypoxia may lead to acquired defects in sinonasal Cl - transport in a fashion likely to confer mucociliary dysfunction in chronic rhinosinusitis. © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.
  • Digital Object Identifier (doi)

    Author List

  • Blount A; Zhang S; Chestnut M; Hixon B; Skinner D; Sorscher EJ; Woodworth BA
  • Start Page

  • 1929
  • End Page

  • 1934
  • Volume

  • 121
  • Issue

  • 9