suppression of adenosine-activated chloride transport by ethanol in airway epithelia抑制adenosine-activated氯运输乙醇在气道上皮细胞.pdf

Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia 1 1,2,3 Sammeta V. Raju , Guoshun Wang * 1 Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America, 2 Department of Microbiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America, 3 Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America Abstract Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (ISC) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A2B adenosine receptor (A2BAR), largely abolished the adenosine-stimulated chloride transport, suggesting that A2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to bl