High mobility group box 1 release from cholangiocytes in patients with acute-on-chronic liver failure

被引:9
作者
Xu, Heng [1 ,2 ]
Li, Hongxia [1 ]
Qu, Yachao [1 ]
Zheng, Junfu [1 ]
Lu, Jun [1 ]
机构
[1] Capital Med Univ, Beijing Youan Hosp, Hepatol & Canc Biotherapy Ward, Beijing 100069, Peoples R China
[2] Anhui Med Univ, Dept Pathophysiol, Hefei 230032, Anhui, Peoples R China
关键词
high mobility group box 1; proinflammatory cytokine; acute-on-chronic liver failure; cholangiocytes; INFLAMMATORY RESPONSE SYNDROME; NECROTIC CELLS; HMGB1; DISEASE; PROTEIN; SEPSIS; CHROMOSOMAL-PROTEIN-1; PATHOGENESIS; EXPRESSION; CIRRHOSIS;
D O I
10.3892/etm.2014.1904
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
High mobility group box chromosomal protein 1 (HMGB1) is an important proinflammatory molecule in a number of inflammatory disorders, but little is known about its role in acute-on-chronic liver failure (ACLF). To elucidate the role of HMGB1 in ACLF, the expression of HMGB1 in liver specimens from patients with ACLF was investigated. Immunohistochemical staining was performed to confirm the expression and subcellular localization of HMGB1 in liver specimens obtained from 13 patients With ACLF caused by hepatitis B virus (HBV) infection, 20 patients with chronic viral hepatitis B and 20 healthy controls. In addition, TFK-1 cells (human cholangiocarcinoma cell line) were stimulated with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha. The extracellular level of HMGB1 in the culture medium was then determined by ELISA, and cell viability was also examined. In patients with ACLF caused by HBV infection, HMGB1 was found mainly in the cholangiocytes, and cytoplasmic translocation was observed in the cholangiocytes in the liver specimens. In the TFK-1 cell cultures, HMGB1 levels gradually increased from as early as 4 h after stimulation with LPS or TNF-alpha until the end of the stimulation. LPS and TNF-alpha actively induced the cytoplasmic translocation of the HMGB1 protein in TFK-1 cells. These data suggest that HMGB1 plays a critical role in the systemic inflammation associated with ACLF.
引用
收藏
页码:1178 / 1184
页数:7
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