Premium
Transepithelial ion transport is suppressed in hypoxic sinonasal epithelium
Author(s) -
Blount Angela,
Zhang Shaoyan,
Chestnut Michael,
Hixon Brian,
Skinner Daniel,
Sorscher Eric J.,
Woodworth Bradford A.
Publication year - 2011
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.21921
Subject(s) - cystic fibrosis transmembrane conductance regulator , ion transporter , epithelium , messenger rna , cystic fibrosis , forskolin , mucociliary clearance , ussing chamber , epithelial sodium channel , respiratory epithelium , chemistry , medicine , endocrinology , microbiology and biotechnology , respiratory system , reverse transcription polymerase chain reaction , transepithelial potential difference , biology , in vitro , pathology , sodium , biochemistry , lung , gene , organic chemistry , membrane
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.