title: Blockade of high-mobility group box-1 ameliorates acute on chronic liver failure in rats.
abstract: OBJECTIVE
  High-mobility group box-1 (HMGB1) is identified as an extracellularly released mediator of inflammation. In this study, specific monoclonal anti-HMGB1 antibody was administered to rats with acute on chronic liver failure (ACLF) in order to evaluate the therapeutic efficacy of HMGB1 blockade.
  
  
  METHODS
  All animals were randomly divided into control group, model group and anti-HMGB1 antibody group. The changes in liver histology and apoptosis of liver tissue were detected by H&E staining and TUNEL assay, respectively. The serum levels of alanine aminotransferase (ALT), endotoxin, HMGB1, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were examined. The hepatic levels of HMGB1, caspase3, Toll-like receptor 4 (TLR4) and p65 subunit of NF-κB (P65) were also determined.
  
  
  RESULTS
  Changes in liver pathology and liver cell apoptosis were greatly attenuated in the anti-HMGB1 antibody group compared with the model group. The serum levels of ALT, endotoxin, TNF-α, IFN-γ and HMGB1 were also decreased in the anti-HMGB1 antibody group. Furthermore, the hepatic levels of HMGB1, TLR4, caspase3 and P65 were also down-regulated by HMGB1 blockade.
  
  
  CONCLUSIONS
  Blockade of HMGB1 can confer a protective effect against ACLF in rats, even 24 h after induction of ACLF. The protective effect of HMGB1 blockade is associated with interactions of HMGB1 with the TLR4 signaling pathway and cytokine production.
authors.affiliation: Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.forename: Li-Kun
authors.initials: LK
authors.lastname: Wang
authors.forename: Lu-Wen
authors.initials: LW
authors.lastname: Wang
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Han
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Zuo-Jiong
authors.initials: ZJ
authors.lastname: Gong
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D051927:CD24 Antigen; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood; D008070:Lipopolysaccharides; D017093:Liver Failure / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; D051927:CD24 Antigen; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D008070:Lipopolysaccharides; D020011:Protective Agents; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000410:Alanine Transaminase