title: Chronic ingestion of alcohol modulates expression of ubiquitin editing enzyme A20 in lung macrophages.
abstract: BACKGROUND
  Alcohol abuse is involved in the pathogenesis of multiple organ disorders; the underlying mechanism is incompletely understood. The ubiquitin editing enzyme A20 is involved in regulating activities in the cell. Suppression of A20 is suggested as one factor in the initiation of inflammation. This study investigates the mechanism by which chronic alcohol consumption modulates the levels of ubiquitin editing enzyme A20 in macrophages and further contributes to induce endothelial barrier dysfunction in the lung.
  
  
  METHODS
  Mice were gavage-fed with 40% alcohol daily for 0-3 weeks. Airway macrophages were collected by lung lavage. Expression of ubiquitin editing enzyme A20 in isolated macrophages was assessed at both mRNA and protein levels. The endothelial barrier function of the lung was evaluated by the Evans blue method.
  
  
  RESULTS
  Mice treated with alcohol for 3 weeks showed an increase in cell infiltration in the lung in response to exposure to peptidoglycan; over 80% of the infiltrated cells were macrophages. Furthermore, we observed that A20 level was suppressed in macrophages of mice treated with alcohol; the levels of tumor necrosis factor, interleukin-6 and nuclear factor kappa B in macrophage were increased. In addition, the endothelial barrier function of the lung was compromised, showing excessive infiltration of Evans blue in the lung indicating lung edema. Pretreatment with synthesized A20 inhibited alcohol-induced lung endothelial barrier dysfunction.
  
  
  CONCLUSIONS
  We conclude that chronic alcohol ingestion disturbs the endothelial barrier function in the lung by modulating macrophage properties. Increase in A20 in the cell may have potential for the treatment of inflammatory disorders.
authors.affiliation: Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. liushuiping66@gmail.com.
authors.forename: Quan-Yong
authors.initials: QY
authors.lastname: Huang
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Chen
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: Liu