title: Effects of chronic ethanol ingestion on tight junction proteins and barrier function of alveolar epithelium in the rat.
abstract: Previous studies show that chronic alcohol abuse is an independent risk factor for acute lung injury (ALI) and impairs alveolar epithelial barrier function through glutathione depletion. However, the precise molecular structures that are damaged by chronic ethanol ingestion have not been identified. To test whether chronic ethanol ingestion impairs the alveolar epithelium barrier by tight junction protein deterioration and predisposes to ALI, this study determined the alterations in tight junction proteins occludin, zonula occludens (ZO)-1, and adherens junction protein E-cadherin in alveolar epithelium and observed the protective effect of glutamine (Gln) supplementation. Sixty Sprague-Dawley rats were assigned to control, ethanol (6 weeks' ethanol feeding), lipopolysaccharide ([LPS] 2 mg/kg, i.v.), ethanol plus LPS, ethanol plus Gln (0.3 g/kg, gavage daily), and ethanol plus Gln plus LPS groups. Treatment with both ethanol and LPS significantly increased bronchoalveolar epithelial permeability, and treatment with ethanol plus LPS further increased the permeability. Using immunofluorescence, immunoblotting, and reverse transcriptase-polymerase chain reaction, this study shows that treatment with both ethanol and LPS induced partial breakdown of membrane staining and decreased cytoplasm staining in alveolar epithelium and decreased the messenger RNA and protein expression of those molecules in alveolar epithelial cells. Treatment with ethanol plus LPS caused further deterioration. Moreover, Gln supplementation markedly attenuated the enhanced bronchoalveolar epithelial permeability and decreased messenger RNA and protein expression of those molecules induced by ethanol and ethanol plus LPS. These data suggest that chronic ethanol ingestion impairs the alveolar epithelial barrier function via occludin, ZO-1, and E-cadherin deterioration, and predisposes to ALI. Glutamine supplementation has protective effect.
authors.affiliation: Division of Pulmonary Medicine, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, China. zhangyuanly@126.com
authors.forename: Yuan-Li
authors.initials: YL
authors.lastname: Zhang
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Jiong
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009994:Osmolar Concentration; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D000431:Ethanol