title: HMGB1 cytoplasmic translocation in patients with acute liver failure.
abstract: BACKGROUND
  High-mobility group box 1 (HMGB1) is a late mediator of lethal systemic inflammation. Acute liver failure (ALF) has been shown to trigger systemic inflammation in clinical and animal studies. To evaluate the possibility of HMGB1 cytoplasmic translocation in ALF, we determined whether HMGB1 is released in hepatocytes and end organ in patients with liver failure/injury.
  
  
  METHODS
  HepG2 cell were stimulated with LPS or TNF-α, the increase of HMGB1 extracellularly in the culture medium and intracellularly in various cellular fractions were determined by western blot or immunocytochemistry. To observe sub-cellular location of HMGB1 in hepatocytes, liver specimens were obtained from 6 patients with ALF caused by HBV infection, 10 patients with chronic viral hepatitis B, 6 healthy controls, as well as animals model of ALF by intraperitoneal administration of D-GalN (600 mg/kg) and LPS (0.5 mg/kg).
  
  
  RESULTS
  In HepG2 cell culture, LPS or TNF actively induced HMGB1 cytoplasmic translocation and release in a time- and dose-dependent fashion. In animal model of ALF, cytoplasmic HMGB1 translocation was observed in hepatocyts as early as 3 hours post onset of ALF. In patients with ALF caused by HBV infection, cytoplasmic HMGB1 translocation was similarly observed in some hepatocytes of the liver specimen.
  
  
  CONCLUSIONS
  Cytoplasmic HMGB1 translocation may occur during ALF, which may potentially contribute to the pathogenesis of liver inflammatory diseases.
authors.affiliation: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, PR China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Zhou
authors.forename: Shu-Shan
authors.initials: SS
authors.lastname: Zhao
authors.forename: Ming-Xiang
authors.initials: MX
authors.lastname: Zou
authors.forename: Pan
authors.initials: P
authors.lastname: Zhang
authors.forename: Bao-Xing
authors.initials: BX
authors.lastname: Zhang
authors.forename: Xia-Hong
authors.initials: XH
authors.lastname: Dai
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Liu
authors.forename: Haichao
authors.initials: H
authors.lastname: Wang
authors.forename: Xue-Gong
authors.initials: XG
authors.lastname: Fan
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D006509:Hepatitis B / Q000150:complications; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000494:pharmacology; D017114:Liver Failure, Acute / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha