Circulating Histones Exacerbate Inflammation in Mice With Acute Liver Failure
Circulating Histones Exacerbate Inflammation in Mice With Acute Liver Failure
复制标题
循环组蛋白加剧急性肝衰竭小鼠的炎症
DOI：
10.1002/jcb.24588
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发表时间：
2013-10-01
影响因子：
4
通讯作者：
Wen, Tao
中科院分区：
文献类型：
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作者：
Wen, Zongmei;Liu, Yan;Wen, Tao
循环组蛋白是一种新发现的与多种炎症性疾病有关的介质。在急性肝衰竭（ALF）过程中，组蛋白从垂死的肝细胞或炎性白细胞释放到循环中可能引发并放大炎症。在这项研究中，我们研究了循环组蛋白在D-半乳糖胺（GalN）加脂多糖（LPS）诱导的ALF小鼠模型中的假定致病作用。测定GalN/LPS处理小鼠的肝功能和组织学指标、髓过氧化物酶（MPO）活性、肝细胞凋亡和循环组蛋白水平。GalN/LPS引起严重的肝损伤和循环组蛋白血浆浓度的显著增加。为了进一步评估循环组蛋白在我们模型中的作用，我们给予外源性组蛋白和抗组蛋白H4抗体。值得注意的是，外源性组蛋白加重GalN/LPS诱导的肝毒性，而抗组蛋白抗体显著保护小鼠。循环中的组蛋白既可以作为ALF活性的功能性标志物，也可以作为促进ALF进展的炎症介质。阻断循环组蛋白显示出强有力的保护作用，提示ALF的潜在治疗策略。J.细胞。114：2384-2391，2013中。© 2013 Wiley Periodicals，Inc.
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.