期刊
FEBS JOURNAL
卷 280, 期 6, 页码 1409-1419出版社
WILEY
DOI: 10.1111/febs.12132
关键词
d-(+)-galactosamine hydrochloride (d-GalN); high-mobility group box1 (HMGB1); lipopolysaccharide (LPS); synergistic effect; tumor necrosis factor- (TNF-)
资金
- National Natural Science Foundation of China [30470364]
High-mobility group box1 (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- (TNF-), interleukin-6, inducible nitric oxide synthase, and tissue factor. TNF- and HMGB1 form a positive feedback loop to amplify the downstream signals. mAbs against HMGB1 and TNF- 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- to promote pathological processes in acute liver failure.
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