Ethanol treatment reduces bovine bronchial epithelial cell migration.
BACKGROUND
Chronic ethanol abuse is associated with significant lung disease. Excessive alcohol intake increases risk for a variety of respiratory tract diseases, including pneumonia and bronchitis. Damage to airway epithelium is critical to the pathogenesis of airway disorders such as chronic bronchitis and chronic obstructive pulmonary disease. The ability of the airway epithelium to repair itself is an important step in the resolution of airway inflammation and disease. Ethanol exposure is known to modulate signaling systems in bronchial epithelial cells. We hypothesize that chronic ethanol exposure down-regulates the adenosine 3':5'-cyclic monophosphate signaling cascade in airway epithelial cells, resulting in decreased epithelial cell migration and repair.


METHODS
We evaluated the effect of ethanol on primary cultures of bovine bronchial epithelial cells in in vitro models of cell migration, wound repair, cell attachment, and cell spreading.


RESULTS
Ethanol causes a concentration-dependent effect on closure of mechanical wounds in cell monolayers. Pretreatment of cells with 100 mm ethanol for 24 hr further slows wound closure. Ethanol pretreatment also reduced the protein kinase A response to wounding and made the cells unresponsive to stimuli of protein kinase A that accelerate wound closure. The effects of ethanol on cell migration in wound closure were confirmed in another assay of migration, the Boyden chamber cell migration assay. Prolonged treatment with ethanol also reduced other cell functions, such as spreading and attachment, which are necessary for epithelial repair.


CONCLUSIONS
Ethanol modulates signaling systems that are relevant to airway injury and repair, suggesting that chronic, heavy ethanol ingestion has a detrimental impact on airway repair. Impaired response to inflammation and injury may contribute to chronic airway disease.
Spurzem
John R
JR
Department of Internal Medicine, Omaha Veterans Affairs Medical Center, Omaha, Nebraska 68198-5300, USA. jspurzem@unmc.edu
Veys
Tom
T
Devasure
Jane
J
Sisson
Joseph H
JH
Wyatt
Todd A
TA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014945:Wound Healing
D000318:Adrenergic beta-Agonists; D002492:Central Nervous System Depressants; D000431:Ethanol; D003094:Collagen; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol