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Blockade of high-mobility group box-1 ameliorates acute on chronic liver failure in rats

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Abstract

Objective

High-mobility group box-1 (HMGB1) is identified as an extracellularly released mediator of inflammation. In this study, specific monoclonal anti-HMGB1 antibody was administered to rats with acute on chronic liver failure (ACLF) in order to evaluate the therapeutic efficacy of HMGB1 blockade.

Methods

All animals were randomly divided into control group, model group and anti-HMGB1 antibody group. The changes in liver histology and apoptosis of liver tissue were detected by H&E staining and TUNEL assay, respectively. The serum levels of alanine aminotransferase (ALT), endotoxin, HMGB1, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were examined. The hepatic levels of HMGB1, caspase3, Toll-like receptor 4 (TLR4) and p65 subunit of NF-κB (P65) were also determined.

Results

Changes in liver pathology and liver cell apoptosis were greatly attenuated in the anti-HMGB1 antibody group compared with the model group. The serum levels of ALT, endotoxin, TNF-α, IFN-γ and HMGB1 were also decreased in the anti-HMGB1 antibody group. Furthermore, the hepatic levels of HMGB1, TLR4, caspase3 and P65 were also down-regulated by HMGB1 blockade.

Conclusion

Blockade of HMGB1 can confer a protective effect against ACLF in rats, even 24 h after induction of ACLF. The protective effect of HMGB1 blockade is associated with interactions of HMGB1 with the TLR4 signaling pathway and cytokine production.

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Acknowledgments

This study was supported by a grant from the National Natural Science Foundation of China (No. 81071342).

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Authors and Affiliations

  1. Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, 430060, China

    Xun Li, Li-Kun Wang, Lu-Wen Wang, Xiao-Qun Han, Fan Yang & Zuo-Jiong Gong

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  1. Xun Li
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  2. Li-Kun Wang
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  3. Lu-Wen Wang
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Correspondence to Zuo-Jiong Gong.

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Responsible Editor: Mauro Teixeira.

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Li, X., Wang, LK., Wang, LW. et al. Blockade of high-mobility group box-1 ameliorates acute on chronic liver failure in rats. Inflamm. Res. 62, 703–709 (2013). https://doi.org/10.1007/s00011-013-0624-1

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  • DOI: https://doi.org/10.1007/s00011-013-0624-1

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