Open AccessCFTR Modulation by the Tobacco Smoke Toxin Acrolein
Author(s) -
Alexander Nathan S.,
Skinner Daniel,
Sorscher Eric,
Zhang Shaoyan,
Woodworth Bradford A.
Publication year - 2011
Publication title -
otolaryngology–head and neck surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.232
H-Index - 121
eISSN - 1097-6817
pISSN - 0194-5998
DOI - 10.1177/0194599811416318a243
Subject(s) - acrolein , secretion , chemistry , toxin , cytotoxicity , pharmacology , biochemistry , in vitro , biology , catalysis
Objective Tobacco‐smoke exposure inhibits transepithelial Cl‐secretion—a major determinant of airway surface liquid hydration and mucociliary clearance (MCC). The objective of the current study was to evaluate the effects of acrolein exposure (a tobacco smoke toxin) on Cl‐transport through the major apical anion channel CFTR in sinonasal epithelium. Method Primary murine nasal septal (MNSE, wild type, and transgenic CFTR‐/‐) and human sinonasal epithelial (HSNE) cultures were exposed to acrolein in Ussing chambers, and effects on Cl‐secretion were investigated using pharmacologic manipulation. Cellular cAMP signaling and cytotoxicity were also investigated. Results Acrolein‐stimulated Cl‐secretion (ΔISC ‐ change in short‐circuit current in µA/cm2) at low concentrations (100 µM, 15.8 ± 2.2 vs 2.4 ± 0.8 (control); p‐transport at 300 µM (13.3 ± 1.2 vs 19.9 ± 1.0; p‐secretion was solely reliant upon the presence of CFTR (confirmed in transgenic CFTR ‐/‐ MNSE), but independent of cAMP signaling. Inhibition at higher concentrations was not secondary to cellular cytotoxicity, indicating direct effects on the CFTR. Conclusion Decreased MCC is a major contributing feature to chronic rhinosinusitis. The present study demonstrated that acrolein has complex but direct interactions with CFTR. Robust inhibition of Cl‐transport at higher concentrations indicates the potential contribution of this toxin to decreased MCC in individuals with chronic tobacco smoke exposure.