Molecular analysis during con a-induced liver failure suggests the relevance of jun kinase and IRF-1 for hepatocyte injury

The administration of concanavalin A (Con A) induces a rapid severe injury of hepatocytes in mice. Although the Con A–induced hepatitis is considered to be an experimental model of human autoimmune hepatitis, the precise cellular and molecular mechanisms that induce hepatocyte injury remain unclear. Here, we demonstrate that Vα14 NKT cells are required and sufficient for induction of this hepatitis. Moreover, interleukin (IL)-4 produced by Con A–activated Vα14 NKT cells is found to play a crucial role in disease development by augmenting the cytotoxic activity of Vα14 NKT cells in an autocrine fashion. Indeed, short-term treatment with IL-4 induces an increase in the expression of granzyme B and Fas ligand (L) in Vα14 NKT cells. Moreover, Vα14 NKT cells from either perforin knock-out mice or FasL-mutant gld/gld mice fail to induce hepatitis, and hence perforin–granzyme B and FasL appear to be effector molecules in Con A–induced Vα14 NKT cell–mediated hepatocyte injury.

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The role of intracellular high-mobility group box 1 in the early activation of Kupffer cells and the development of Con A-induced acute liver failure

Immunobiology ◽

10.1016/j.imbio.2013.04.011 ◽

2013 ◽

Vol 218 (10) ◽

pp. 1284-1292 ◽

Cited By ~ 19

Author(s):

Qiao Yang ◽

Yanning Liu ◽

Yu Shi ◽

Min Zheng ◽

Jiliang He ◽

...

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

Kupffer Cells ◽

High Mobility ◽

High Mobility Group ◽

Con A ◽

Early Activation

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HBx facilitates ferroptosis in acute liver failure via EZH2 mediated SLC7A11 suppression

Journal of Biomedical Science ◽

10.1186/s12929-021-00762-2 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Guo-Zhen Liu ◽

Xu-Wen Xu ◽

Shu-Hui Tao ◽

Ming-Jian Gao ◽

Zhou-Hua Hou

Keyword(s):

Liver Failure ◽

Acute Liver Failure ◽

Epigenetic Modification ◽

Hbv Infection ◽

High Rate ◽

Mice Model ◽

Primary Hepatocytes ◽

Hepatocyte Injury

Abstract Background Acute liver failure (ALF) is a syndrome of severe hepatocyte injury with high rate of mortality. Hepatitis B virus (HBV) infection is the major cause of ALF worldwide, however, the underlying mechanism by which HBV infection leads to ALF has not been fully disclosed. Methods D-GalN-induced hepatocyte injury model and LPS/D-GalN-induced ALF mice model were used to investigate the effects of HBV X protein (HBx) in vitro and in vivo, respectively. Cell viability and the levels of Glutathione (GSH), malondialdehyde (MDA) and iron were measured using commercial kits. The expression of ferroptosis-related molecules were detected by qRT-PCR and western blotting. Epigenetic modification and protein interaction were detected by chromatin immunoprecipitation (ChIP) assay and co-immunoprecipitation (co-IP), respectively. Mouse liver function was assessed by measuring aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The histological changes in liver tissues were monitored by hematoxylin and eosin (H&E) staining, and SLC7A11 immunoreactivity was assessed by immunohistochemistry (IHC) analysis. Results D-GalN triggered ferroptosis in primary hepatocytes. HBx potentiated D-GalN-induced hepatotoxicity and ferroptosis in vitro, and it suppressed SLC7A11 expression through H3K27me3 modification by EZH2. In addition, EZH2 inhibition or SLC7A11 overexpression attenuated the effects of HBx on D-GalN-induced ferroptosis in primary hepatocytes. The ferroptosis inhibitor ferrostatin-1 (Fer-1) protected against ALF and ferroptosis in vivo. By contrast, HBx exacerbates LPS/D-GalN-induced ALF and ferroptosis in HBx transgenic (HBx-Tg) mice. Conclusion HBx facilitates ferroptosis in ALF via EZH2/H3K27me3-mediated SLC7A11 suppression.

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Lectin Binding Studies on RNA Tumor Virus-Infected Cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100115250 ◽

1975 ◽

Vol 33 ◽

pp. 326-327

Author(s):

D. C. Hixson

Keyword(s):

Binding Sites ◽

Lectin Binding ◽

Culture Conditions ◽

3T3 Cells ◽

Binding Studies ◽

Con A ◽

Microscopic Studies ◽

Tumor Virus ◽

Infected Cells ◽

Cell Culture Conditions

The abilities of plant lectins to preferentially agglutinate malignant cells and to bind to specific monosaccharide or oligosaccharide sequences of glycoproteins and glycolipids make them a new and important biochemical probe for investigating alterations in plasma membrane structure which may result from malignant transformation. Electron and light microscopic studies have demonstrated clustered binding sites on surfaces of SV40-infected or tryp- sinized 3T3 cells when labeled with concanavalin A (con A). No clustering of con A binding sites was observed in normal 3T3 cells. It has been proposed that topological rearrangement of lectin binding sites into clusters enables con A to agglutinate SV40-infected or trypsinized 3T3 cells (1). However, observations by other investigators have not been consistent with this proposal (2) perhaps due to differences in reagents used, cell culture conditions, or labeling techniques. The present work was undertaken to study the lectin binding properties of normal and RNA tumor virus-infected cells and their associated viruses using lectins and ferritin-conjugated lectins of five different specificities.

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