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Journal of Cellular Biochemistry

Circulating histones exacerbate inflammation in mice with acute liver failure

Authors

  • Zongmei Wen,

    1. Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, P.R. China
    2. Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, P.R. China
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  • Yan Liu,

    1. Department of Liver Diseases, Beijing Youan Hospital Affiliated with Capital Medical University, Beijing, P.R. China
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  • Feng Li,

    1. Department of Surgery, Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas
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  • Feng Ren,

    1. Beijing Institute of Hepatology, Beijing, P.R. China
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  • Dexi Chen,

    1. Department of Liver Diseases, Beijing Youan Hospital Affiliated with Capital Medical University, Beijing, P.R. China
    2. Beijing Institute of Hepatology, Beijing, P.R. China
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  • Xiuhui Li,

    Corresponding author
    1. Institute of Infectious Diseases for Traditional Chinese and Western Integrative Medicine, Beijing, P.R. China
    • Department of Liver Diseases, Beijing Youan Hospital Affiliated with Capital Medical University, Beijing, P.R. China
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  • Tao Wen

    1. Department of Liver Diseases, Beijing Youan Hospital Affiliated with Capital Medical University, Beijing, P.R. China
    2. Beijing Institute of Hepatology, Beijing, P.R. China
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  • The authors have declared that there are no competing interests.
  • Zongmei Wen and Yan Liu are co-first authors.
  • Xiuhui Li and Tao Wen contribute equally to this work.

Correspondence to: Xiuhui Li and Tao Wen, Beijing Institute of Hepatology; Department of Liver Diseases, Beijing Youan Hospital Affiliated with Capital Medical University, 8 Xitoutiao, Youanmen Wai, Fengtai District, Beijng 100069, P.R. China.

E-mail: lixiuhui@sohu.com (X.L.), wentao5281@163.com (T.W.)

Abstract

Circulating histones are a newly recognized mediator implicated in various inflammatory diseases. It is likely that the release of histones, from dying hepatocytes or inflammatory leukocytes, into the circulation initiates and amplifies inflammation during the course of acute liver failure (ALF). In this study, we investigated a putative pathogenic role of circulating histones in a murine model of ALF induced by D-galactosamine (GalN) plus lipopolysaccharide (LPS). Hepatic function and histological indexes, myeloperoxidase (MPO) activity, hepatocyte apoptosis and the levels of circulating histone were measured in GalN/LPS-treated mice. GalN/LPS caused severe liver damage and a notable increase in plasma concentration of circulating histones. To further assess the role of circulating histones in our model, we administered exogenous histones and anti-histone H4 antibody. Notably, exogenous histones aggravated GalN/LPS-induced hepatotoxicity, whereas anti-histone antibody significantly protected mice. Circulating histones may serve as both a functional marker of ALF activity and as an inflammatory mediator contributing to the progression of ALF. Blockade of circulating histones shows potent protective effects, suggesting a potential therapeutic strategy for ALF. J. Cell. Biochem. 114: 2384–2391, 2013. © 2013 Wiley Periodicals, Inc.

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