title: Synergistic effects of antibodies against high-mobility group box 1 and tumor necrosis factor-α antibodies on D-(+)-galactosamine hydrochloride/lipopolysaccharide-induced acute liver failure.
abstract: High-mobility group box 1 (HMGB1) protein is released into the serum after tissue damage, and serves as a warning signal to enhance the inflammatory response. Acute liver injury is one of the diseases that starts with tissue damage and ends with systemic inflammation. We used D-(+)-galactosamine hydrochloride (D-GalN)/lipopolysaccharide (LPS)-treated mice as an acute liver injury model to explore the functions of HMGB1 in more detail. HMGB1 is released into the serum at a very early stage of D-GalN/LPS-induced acute liver injury. It upregulates the expression of tumor necrosis factor-α (TNF-α), interleukin-6, inducible nitric oxide synthase, and tissue factor. TNF-α and HMGB1 form a positive feedback loop to amplify the downstream signals. mAbs against HMGB1 and TNF-α have synergistic effects in protecting mice from D-GalN/LPS-induced acute liver failure. The results suggest that HMGB1 is a key mediator in D-GalN/LPS-induced acute liver injury. Tissue damage and cell necrosis shortly after administration of D-GalN and LPS lead to early HMGB1 release, and HMGB1 acts synergistically with TNF-α to promote pathological processes in acute liver failure.
authors: Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors: Wei
authors: W
authors: Wang
authors: Li
authors: L
authors: Sun
authors: Yonghao
authors: Y
authors: Deng
authors: Jie
authors: J
authors: Tang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D004357:Drug Synergism; D005260:Female; D005688:Galactosamine / Q000009:adverse effects; D024243:HMGB1 Protein / Q000097:blood / Q000276:immunology*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017114:Liver Failure, Acute / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000276:immunology / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D025941:Protein Interaction Mapping; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D024243:HMGB1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D005688:Galactosamine; D052247:Nitric Oxide Synthase Type II; D000410:Alanine Transaminase