The authors have declared that there are no competing interests.
Circulating histones exacerbate inflammation in mice with acute liver failure
Article first published online: 15 AUG 2013
Copyright © 2013 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 10, pages 2384–2391, October 2013
How to Cite
Wen, Z., Liu, Y., Li, F., Ren, F., Chen, D., Li, X. and Wen, T. (2013), Circulating histones exacerbate inflammation in mice with acute liver failure. J. Cell. Biochem., 114: 2384–2391. doi: 10.1002/jcb.24588
Zongmei Wen and Yan Liu are co-first authors.
Xiuhui Li and Tao Wen contribute equally to this work.
- Issue published online: 15 AUG 2013
- Article first published online: 15 AUG 2013
- Accepted manuscript online: 20 MAY 2013 09:56AM EST
- Manuscript Accepted: 1 MAY 2013
- Manuscript Received: 14 DEC 2012
- National Natural Science Foundation. Grant Numbers: 81241060, 81270532
- Capital Medical University Basic & Clinical Collaborative Project. Grant Number: 12JL14
- Key Project of the National Eleventh-Five Year Research Program of China. Grant Number: 2008ZX10005-007
- Beijing Natural Science Foundation. Grant Number: 7132105
- CIRCULATING HISTONE;
- ACUTE LIVER FAILURE;
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.