Transforming growth factor beta1 expression and activation is increased in the alcoholic rat lung.
Alcohol abuse increases the incidence of acute respiratory distress syndrome more than threefold in patients with septic shock. We have shown that chronic ethanol ingestion in a rat model impairs alveolar epithelial barrier function and enhances lung injury during sepsis. We speculated that transforming growth factor beta(1) (TGFbeta(1)), a pluripotent cytokine implicated in models of epithelial barrier disruption and lung injury, could mediate alveolar epithelial injury in the alcoholic lung. We report that chronic ethanol ingestion (6 weeks) in rats increased both TGFbeta(1) mRNA and protein tissue expression (p < 0.05), but alone did not induce the release of TGFbeta(1) into the alveolar space. However, during endotoxemia, ethanol-fed rats released fivefold more TGFbeta(1) protein (by ELISA, p < 0.05) into the alveolar space than control-fed rats. Furthermore, lung lavage fluid from endotoxemic, ethanol-fed rats had more biologically active TGFbeta(1) protein than control-fed rats (p < 0.05), as reflected by anti-TGFbeta(1) antibody-inhibitable induction of permeability in rat alveolar epithelial monolayers in vitro. We conclude that chronic ethanol ingestion increases lung expression of TGFbeta(1,) which, during endotoxemia, is released and activated in the alveolar space in which it can disrupt the normally tight epithelial barrier. We speculate that this mechanism could contribute to the increased risk of acute respiratory distress syndrome in alcoholic patients.
Bechara
Rabih I
RI
Section of Pulmonary and Critical Care Medicine, Decatur, GA, USA.
Brown
Lou Ann S
LA
Roman
Jesse
J
Joshi
Pratibha C
PC
Guidot
David M
DM
D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000276:immunology; D000431:Ethanol / Q000633:toxicity*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051381:Rats; D012016:Reference Values; D020545:Respiratory Mucosa / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000431:Ethanol