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. (14th February 2013)

• Record Type: Journal Article
• Authors: Wang, Wei; Sun, Li; Deng, Yonghao; Tang, Jie
• Is Part Of: FEBS journal. Volume 280:Number 6(2013)
• Page Start: 1409
• Page End: 1419
• Publication Date: 2013-02-14
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.12132
• Languages: English
• ISSNs: 1742-464X

Abstract

<abstract abstract-type="main" id="febs12132-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <sc>d</sc>‐(+)‐galactosamine hydrochloride (<sc>d</sc>‐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 <sc>d</sc>‐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 <sc>d</sc>‐GalN/LPS‐induced acute liver failure. The results suggest that HMGB1 is a key mediator in <sc>d</sc>‐GalN/LPS‐induced acute liver injury. Tissue damage and cell necrosis shortly after administration of <sc>d</sc>‐GalN and LPS lead to early HMGB1 release, and HMGB1 acts synergistically with TNF‐α to promote pathological processes in acute liver failure.</p> </abstract>