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Circulating histones exacerbate inflammation in mice with acute liver failure
Author(s) -
Wen Zongmei,
Liu Yan,
Li Feng,
Ren Feng,
Chen Dexi,
Li Xiuhui,
Wen Tao
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24588
Subject(s) - histone , lipopolysaccharide , inflammation , myeloperoxidase , hepatocyte , apoptosis , chemistry , antibody , immunology , biology , biochemistry , in vitro , gene
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.