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Open Access Research article

HMGB1 cytoplasmic translocation in patients with acute liver failure

Rong-Rong Zhou1, Shu-Shan Zhao12, Ming-Xiang Zou3, Pan Zhang1, Bao-Xing Zhang1, Xia-Hong Dai1, Ning Li4, Hong-Bo Liu1, Haichao Wang5 and Xue-Gong Fan1*

Author Affiliations

1 Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China

2 Eight-year Program, Central South University, Changsha, 410008, Hunan, PR China

3 Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China

4 Department of Blood transfusion, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, PR China

5 Department of Emergency Medicine, North Shore University Hospital-New York University School of Medicine, Manhasset, New York, 11030, USA

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BMC Gastroenterology 2011, 11:21  doi:10.1186/1471-230X-11-21

Published: 15 March 2011

Abstract

Background

High-mobility group box 1 (HMGB1) is a late mediator of lethal systemic inflammation. Acute liver failure (ALF) has been shown to trigger systemic inflammation in clinical and animal studies. To evaluate the possibility of HMGB1 cytoplasmic translocation in ALF, we determined whether HMGB1 is released in hepatocytes and end organ in patients with liver failure/injury.

Methods

HepG2 cell were stimulated with LPS or TNF-α, the increase of HMGB1 extracellularly in the culture medium and intracellularly in various cellular fractions were determined by western blot or immunocytochemistry. To observe sub-cellular location of HMGB1 in hepatocytes, liver specimens were obtained from 6 patients with ALF caused by HBV infection, 10 patients with chronic viral hepatitis B, 6 healthy controls, as well as animals model of ALF by intraperitoneal administration of D-GalN (600 mg/kg) and LPS (0.5 mg/kg).

Results

In HepG2 cell culture, LPS or TNF actively induced HMGB1 cytoplasmic translocation and release in a time- and dose-dependent fashion. In animal model of ALF, cytoplasmic HMGB1 translocation was observed in hepatocyts as early as 3 hours post onset of ALF. In patients with ALF caused by HBV infection, cytoplasmic HMGB1 translocation was similarly observed in some hepatocytes of the liver specimen.

Conclusions

Cytoplasmic HMGB1 translocation may occur during ALF, which may potentially contribute to the pathogenesis of liver inflammatory diseases.