title: Chronic liver injury in mice promotes impairment of skin barrier function via tumor necrosis factor-alpha.
abstract: BACKGROUND
  Alcohol is frequently used to induce chronic liver injury in laboratory animals. Alcohol causes oxidative stress in the liver and increases the expression of inflammatory mediators that cause hepatocellular damage. However, during chronic liver injury, it is unclear if/how these liver-derived factors affect distal tissues, such as the skin.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate skin barrier function during chronic liver injury.
  
  
  METHODS
  Hairless mice were administered 5% or 10% ethanol for 8 weeks, and damages to the liver and skin were assessed using histological and protein-analysis methods, as well as by detecting inflammatory mediators in the plasma.
  
  
  RESULTS
  After alcohol administration, the plasma concentration of the aspartate and alanine aminotransferases increased, while albumin levels decreased. In mice with alcohol-induced liver injury, transepidermal water loss was significantly increased, and skin hydration decreased concurrent with ceramide and type I collagen degradation. The plasma concentrations of [Formula: see text]/[Formula: see text] and tumor necrosis factor-alpha (TNF-α) were significantly increased in mice with induced liver injury. TNF receptor (TNFR) 2 expression was upregulated in the skin of alcohol-administered mice, while TNFR1 levels remained constant. Interestingly, the impairment of skin barrier function in mice administered with 10% ethanol was ameliorated by administering an anti-TNF-α antibody.
  
  
  CONCLUSIONS
  We propose a novel mechanism whereby plasma TNF-α, via TNFR2 alone or with TNFR1, plays an important role in skin barrier function during chronic liver disease in these mouse models.
authors.affiliation: a Faculty of Pharmaceutical Sciences , Suzuka University of Medical Science , Suzuka , Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: a Faculty of Pharmaceutical Sciences , Suzuka University of Medical Science , Suzuka , Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramoto
authors.affiliation: a Faculty of Pharmaceutical Sciences , Suzuka University of Medical Science , Suzuka , Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Koyama
authors.affiliation: a Faculty of Pharmaceutical Sciences , Suzuka University of Medical Science , Suzuka , Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ooi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects; D005650:Fumarates / Q000378:metabolism; D008099:Liver; D008812:Mice, Hairless; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D014867:Water / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D005650:Fumarates; D009566:Nitrates; D009573:Nitrites; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; C579481:creatine glycine ethylic ether fumarate; D014867:Water; D000431:Ethanol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Chronic liver injury; skin barrier function; transepidermal water loss; tumor necrosis factor-alpha; type I collagen