Transforming growth factor β expression and activation is in the alcoholic rat lung

Rabih I. Bechara, Lou Ann S. Brown, Jesse Roman, Pratibha C. Joshi, David M. Guidot

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

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 β1 (TGFβ1), 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 TGFβ1 mRNA and protein tissue expression (p < 0.05), but alone did not induce the release of TGFβ1 into the alveolar space. However, during endotoxemia, ethanol-fed rats released fivefold more TGFβ1 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 TGFβ1 protein than control-fed rats (p < 0.05), as reflected by anti-TGFβ1 antibody-inhibitable induction of permeability in rat alveolar epithelial monolayers in vitro. We conclude that chronic ethanol ingestion increases lung expression of TGFβ 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.

Original languageEnglish (US)
Pages (from-to)188-194
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume170
Issue number2
StatePublished - Jul 15 2004
Externally publishedYes

Keywords

  • Acute respiratory distress syndrome
  • Alcoholism
  • Alveolar type II cell
  • Epithelium
  • Sepsis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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