Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, PR China.
BMC Gastroenterol. 2011 Mar 15;11:21. doi: 10.1186/1471-230X-11-21.
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.
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).
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.
Cytoplasmic HMGB1 translocation may occur during ALF, which may potentially contribute to the pathogenesis of liver inflammatory diseases.
高迁移率族蛋白 B1（HMGB1）是一种晚期介导的致命全身炎症的介质。急性肝衰竭（ALF）已被证明在临床和动物研究中触发全身炎症。为了评估 HMGB1 在 ALF 中细胞质易位的可能性，我们确定了 HMGB1 是否在肝衰竭/损伤患者的肝细胞和终末器官中释放。
用 LPS 或 TNF-α刺激 HepG2 细胞，通过 Western blot 或免疫细胞化学法测定细胞培养基中 HMGB1 含量的增加以及各种细胞成分中的细胞内含量。为了观察 HMGB1 在肝细胞中的亚细胞定位，从 6 例由 HBV 感染引起的 ALF 患者、10 例慢性乙型病毒性肝炎患者、6 例健康对照者以及腹腔内给予 D-GalN（600mg/kg）和 LPS（0.5mg/kg）的 ALF 动物模型中获得肝组织标本。
在 HepG2 细胞培养中，LPS 或 TNF 以时间和剂量依赖的方式主动诱导 HMGB1 细胞质易位和释放。在 ALF 动物模型中，早在 ALF 发作后 3 小时，就观察到肝细胞中 HMGB1 的细胞质易位。在由 HBV 感染引起的 ALF 患者中，肝组织标本中的一些肝细胞中也观察到 HMGB1 的细胞质易位。
细胞质 HMGB1 易位可能发生在 ALF 期间，这可能有助于肝脏炎症性疾病的发病机制。
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