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High-mobility group box 1 exacerbates concanavalin A-induced hepatic injury in mice

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Abstract

High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as an early endogenous alarmin of inflammation following injury and as a late mediator of lethality in sepsis. Although HMGB1 has been implicated in acute lung injury, rheumatoid arthritis, and allograft rejection, its role in T-cell mediated hepatitis remains obscure. Here, we investigated the role and the underlying mechanisms of HMGB1 in concanavalin A (Con A) induced hepatic injury. We demonstrate that high levels of HMGB1 were detected in the necrotic area and in the cytoplasm of hepatocytes after Con A treatment. Administration of exogenous recombinant HMGB1 enhanced Con A-induced hepatitis, while blockade of HMGB1 protected animals from T cell-mediated hepatitis as evidenced by decreased serum transaminase, associated with reduced hepatic necrosis and mortality. Blockade of HMGB1 by a neutralizing antibody inhibited proinflammatory cytokine production, NFκB activity, and the late stage of T/NKT cell activation. These finding thus suggest a pivotal factor of HMGB1 in Con A-induced hepatitis. Blockage of extracellular HMGB1 may represent a novel therapeutic strategy to prevent hepatic injury in T cell-mediated hepatitis.

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Acknowledgments

This work was supported by National Development Program (973) for Key Basic Research of China (Grant 2007CB512400), the National Natural Science Foundation of China (Grants 30772039, 81072440), the youth foundation of Hubei Provincial Department of Education (Grant Q20081212) and foundation of Jingzhou Bureau of Science and Technology (Grant 2008PE-15).

Conflicts of interest

The authors declare no conflict of interests related to this study.

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Authors and Affiliations

  1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China

    Quan Gong, Hui Zhang, Li-hua Duan, Xiao-ling Kong, Fang Zheng, Zheng Tan, Ping Xiong, Min Fang & Fei-li Gong

  2. Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 434023, People’s Republic of China

    Quan Gong

  3. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China

    Jun-hua Li, Shan Zhong & Gang Chen

Authors
  1. Quan Gong
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  2. Hui Zhang
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  3. Jun-hua Li
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  4. Li-hua Duan
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  5. Shan Zhong
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  10. Gang Chen
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  11. Min Fang
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  12. Fei-li Gong
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Correspondence to Min Fang or Fei-li Gong.

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Quan Gong and Hui Zhang contributed equally to this work.

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Gong, Q., Zhang, H., Li, Jh. et al. High-mobility group box 1 exacerbates concanavalin A-induced hepatic injury in mice. J Mol Med 88, 1289–1298 (2010). https://doi.org/10.1007/s00109-010-0681-7

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  • DOI: https://doi.org/10.1007/s00109-010-0681-7

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