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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

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

Wei Wang, Li Sun, Yonghao Deng, Jie Tang

FEBS J. 2013 Mar;280(6):1409-19.

PMID: 23331758

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1772038	Galactosamine hydrochloride		1772-03-8	Price

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