title: Activation of NF-κB after chronic ethanol intake and haemorrhagic shock/resuscitation in mice.
abstract: OBJECTIVE
  Chronic ethanol abuse and haemorrhagic shock are major causes of global mortality and, separately, induce profound hepato- and immune-toxic effects via activation of NF-κB. Here, we assessed the effects of chronic ethanol intake upon the pathophysiological derangements after haemorrhagic shock with subsequent resuscitation (H/R), with particular attention to the contribution of NF-κB.
  
  
  METHODS
  Transgenic NF-κB(EGFP) mice, expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-κB cis-elements were fed a Lieber-DeCarli diet containing ethanol (EtOH-diet) or an isocaloric control diet for 4 weeks and were then pairwise subjected to H/R. Liver tissues and peripheral blood were sampled at 2 or 24 h after H/R. Cytokines in blood and tissue and leukocyte activation (as CD11b expression) were measured, along with EGFP as a marker of NF-κB activation.
  
  
  RESULTS
  The EtOH-diet increased mortality at 24 h after H/R and elevated liver injury, associated with an up-regulation of NF-κB-dependent genes and IL-6 release; it also increased production of NF-κB-driven intercellular adhesion molecule 1 (ICAM-1) and EGFP in liver tissue. At 2h after the H/R procedure in ethanol-fed mice we observed the highest proportion of NF-κB activated non-parenchymal cells and an NF-κB-dependent increase in polymorphonuclear leukocyte CD11b expression.
  
  
  CONCLUSIONS
  The EtOH-diet exacerbated liver injury after H/R, accompanying an overwhelming hepatic and systemic immune response. Our findings contribute to evidence implicating NF-κB as a key player in the orchestration of the immune response in haemorrhagic shock patients with a history of chronic ethanol abuse.
authors: Department of Trauma Surgery, Johann Wolfgang Goethe-University, Frankfurt (Main), Germany.
authors: M
authors: M
authors: Maraslioglu
authors: R
authors: R
authors: Weber
authors: S
authors: S
authors: Korff
authors: C
authors: C
authors: Blattner
authors: C
authors: C
authors: Nauck
authors: D
authors: D
authors: Henrich
authors: C
authors: C
authors: Jobin
authors: I
authors: I
authors: Marzi
authors: M
authors: M
authors: Lehnert
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D005235:Fatty Liver, Alcoholic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006439:Hemodynamics; D006529:Hepatomegaly / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009336:Necrosis; D011401:Promoter Regions, Genetic; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D039481:CD11b Antigen; C090509:Icam1 protein, mouse; D015850:Interleukin-6; D016328:NF-kappa B; C485184:enhanced green fluorescent protein; C577686:interleukin-6, mouse; D018799:Intercellular Adhesion Molecule-1; D049452:Green Fluorescent Proteins; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: NF-κB; chronic ethanol; haemorrhage/resuscitation; inflammation; liver injury
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