Suppression of adenosine-activated chloride transport by ethanol in airway epithelia.
Suppression of adenosine-activated chloride transport by ethanol in airway epithelia.
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DOI：
10.1371/journal.pone.0032112
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Raju SV;Wang G
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 block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections.
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DOI：
10.1152/ajplung.2002.282.1.l12
发表时间：
2002-01-01
影响因子：
4.9
作者：
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通讯作者：
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DOI：
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影响因子：
5.1
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