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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
Author(s) -
Wang Wei,
Sun Li,
Deng Yonghao,
Tang Jie
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12132
Subject(s) - lipopolysaccharide , antibody , galactosamine , tumor necrosis factor alpha , hydrochloride , tumor necrosis factor α , chemistry , high mobility group , immunology , pharmacology , medicine , biochemistry , glucosamine , gene
High‐mobility group box 1 ( HMGB 1) 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 ‐ G al N )/lipopolysaccharide ( LPS )‐treated mice as an acute liver injury model to explore the functions of HMGB 1 in more detail. HMGB 1 is released into the serum at a very early stage of d ‐ G al N / 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 HMGB 1 form a positive feedback loop to amplify the downstream signals. mAbs against HMGB 1 and TNF ‐α have synergistic effects in protecting mice from d ‐ G al N / LPS ‐induced acute liver failure. The results suggest that HMGB 1 is a key mediator in d ‐ G al N / LPS ‐induced acute liver injury. Tissue damage and cell necrosis shortly after administration of d ‐ G al N and LPS lead to early HMGB 1 release, and HMGB 1 acts synergistically with TNF ‐α to promote pathological processes in acute liver failure.