Transepithelial ion transport is suppressed in hypoxic sinonasal epithelium
✍ Scribed by Angela Blount; Shaoyan Zhang; Michael Chestnut; Brian Hixon; Daniel Skinner; Eric J. Sorscher; Bradford A. Woodworth
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 501 KB
- Volume
- 121
- Category
- Article
- ISSN
- 0023-852X
No coin nor oath required. For personal study only.
✦ Synopsis
Objectives/Hypothesis: Sinonasal respiratory epithelial mucociliary clearance is dependent on the transepithelial transport of ions such as Cl À . The objectives of the present study were to investigate the role of oxygen restriction in 1) Cl À transport across primary sinonasal epithelial monolayers, 2) expression of the apical Cl À 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 (DI 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 6 0.46 vs. 19.23 6 0.18) and HSNE (19.55 6 0.56 vs. 25.49 6 1.48 [control]; P < .05). TMEM16A (uridine triphosphate-stimulated transport) was inhibited by 48 hours of hypoxic exposure in MNSE (15.92 6 2.87 vs. 51.44 6 3.71 [control]; P < .05) and by 12 hours of hypoxic exposure in HSNE (16.75 6 0.68 vs. 24.15 6 1.35 [control]). Quantitative RT-PCR (reported as relative mRNA levels 6 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 À 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 À transport in a fashion likely to confer mucociliary dysfunction in chronic rhinosinusitis.