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ConA liver

Lily Dara, Zhang-Xu Liu, Neil Kaplowitz
Hepatocyte death, which can be apoptosis or necrosis depending on the context, is a prominent feature of liver disease. The lectin concanavalin A (ConA) activates immune cells, resulting in inflammatory liver injury and hepatocyte necrosis. In this issue of the JCI, Günther et al. demonstrate that the pseudokinase mixed lineage kinase domain-like protein (MLKL) participates in hepatocyte death in ConA injury and that MLKL-mediated death is independent of the receptor-interacting protein kinase RIPK3. RIPK3 was absent in hepatocytes, and MLKL-deficient mice, but not RIPK3-deficient mice, were protected from ConA-induced liver injury...
October 17, 2016: Journal of Clinical Investigation
Xueting Bai, Peixuan Yang, Qiaoling Zhou, Bozhi Cai, Manon Buist-Homan, He Cheng, Jiyang Jiang, Daifei Shen, Lijun Li, Xiajiong Luo, Klaas Nico Faber, Han Moshage, Ganggang Shi
BACKGROUND AND PURPOSE: Liver diseases are mostly accompanied by inflammation and hepatocyte death. Therapeutic approaches targeting both hepatocyte injury and inflammation are not available. Natural compounds are considered as potential treatment for inflammatory liver diseases. Hesperetin, a flavonoid component of citrus fruits has been reported to have anti-inflammatory properties. The aim of this study was to evaluate the cytoprotective and anti-inflammatory properties of hesperetin both in vitro and in models of fulminant hepatitis...
October 7, 2016: British Journal of Pharmacology
Zongmei Wen, Zhen Lei, Lu Yao, Ping Jiang, Tao Gu, Feng Ren, Yan Liu, Chunyan Gou, Xiuhui Li, Tao Wen
Acute liver failure (ALF) is a life-threatening systemic disorder. Here we investigated the impact of circulating histones, recently identified inflammatory mediators, on systemic inflammation and liver injury in murine models and patients with ALF. We analyzed histone levels in blood samples from 62 patients with ALF, 60 patients with chronic liver disease, and 30 healthy volunteers. We incubated patients' sera with human L02 hepatocytes and monocytic U937 cells to assess cellular damage and cytokine production...
2016: Cell Death & Disease
Ming Xiang, Tingting Liu, Wanyue Tan, Hongyu Ren, Hua Li, Junjun Liu, Hui Cao, Qi Cheng, Xiulan Liu, Hucheng Zhu, Yali Tuo, Jianping Wang, Yonghui Zhang
: The central purpose of this study was to investigate therapeutic effects of the botanical derivative kinsenoside (KD) in experimental autoimmune hepatitis (AIH). Treatment with KD substantially reduced hepatic histopathological damage, induced by lymphocyte infiltration and pro-inflammatory cytokines, in ConA-induced T cell-mediated hepatitis, and in dendritic cells loaded with hepatocellular carcinoma cells (DC/Hepa1-6) induced murine AIH. Interactions between immune cells after KD treatment in AIH were detected by anti-CD8 antibody blocking, CD8(+) T cells sorting, and vaccinated mice with KD-pretreated DCs in a DC/Hepa1-6 model...
September 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Gui-Wei He, Claudia Günther, Andreas E Kremer, Veronika Thonn, Kerstin Amann, Christopher Poremba, Markus F Neurath, Stefan Wirtz, Christoph Becker
OBJECTIVES: Autoimmune hepatitis (AIH) is a severe necroinflammatory liver disease associated with significant mortality. Although loss of hepatocytes is generally recognised as a key trigger of liver inflammation and liver failure, the regulation of hepatic cell death causing AIH remains poorly understood. The aim of this study was to identify molecular mechanisms that drive hepatocyte cell death in the pathogenesis of acute liver injury. DESIGN: Acute liver injury was modelled in mice by intravenous administration of concanavalin A (ConA)...
August 26, 2016: Gut
Xiaojun Tang, Jianchun Huang, Hao Xiong, Keyuan Zhang, Chunxia Chen, Xiaojie Wei, Xiaohui Xu, Qiuqiao Xie, Renbin Huang
BACKGROUND: The previous studies have demonstrated that the polysaccharide isolated from Tarphochlamys affinis (PTA) exhibits anti-tumor effect on S180 tumor-bearing mice and protective effects against hepatic injury. METHODS: In this study, we investigated the anti-tumor activity and possible underlying mechanism of PTA on liver cancer using a murine H22 hepatocarcinoma model. RESULTS: PTA was capable of repressing transplanted H22 solid hepatic tumor cell growth in vivo...
2016: Cellular Physiology and Biochemistry
Qiuxia Fu, Shaoduo Yan, Licui Wang, Xiangguo Duan, Lei Wang, Yue Wang, Tao Wu, Xiaohui Wang, Jie An, Yulong Zhang, Qianqian Zhou, Linsheng Zhan
The role of hepatic NK cells in the pathogenesis of HCV-associated hepatic failure is incompletely understood. In this study, we investigated the effect of HCV on ConA-induced immunological hepatic injury and the influence of HCV on hepatic NK cell activation in the liver after ConA administration. An immunocompetent HCV mouse model that encodes the entire viral polyprotein in a liver-specific manner based on hydrodynamic injection and φC31o integrase was used to study the role of hepatic NK cells. Interestingly, the frequency of hepatic NK cells was reduced in HCV mice, whereas the levels of other intrahepatic lymphocytes remained unaltered...
August 4, 2016: Oncotarget
Wei Zheng, Qilan Wang, Xiaohua Lu, Qiangqiang Shi, Junhui Zou, Yanduo Tao, Pu Wang
Dracocephalum heterophyllum (DH) is a Chinese herbal medicine used in treating hepatitis. However, the protective effects and pharmacological mechanisms of DH in hepatitis are unknown. In this study, we found that pretreatment with DH extract significantly ameliorated liver injury and suppressed the production of inflammatory cytokines, including tumor necrosis factor (TNF-α) and interferon-γ (IFN-γ) in Concanavalin A- (ConA-) induced hepatitis (CIH). DH recruited more CD11b(+) Gr1(+) myeloid-derived suppressor cells (MDSCs) to the liver and suppressed infiltration of macrophages (Kupffer cells) in the liver...
2016: Mediators of Inflammation
Kerstin H Mair, Maria Stadler, Stephanie C Talker, Hilde Forberg, Anne K Storset, Andrea Müllebner, J Catharina Duvigneau, Sabine E Hammer, Armin Saalmüller, Wilhelm Gerner
The CD3(-)NKp46(+) phenotype is frequently used for the identification of natural killer (NK) cells in various mammalian species. Recently, NKp46 expression was analyzed in more detail in swine. It could be shown that besides CD3(-)NKp46(+) lymphocytes, a small but distinct population of CD3(+)NKp46(+) cells exists. In this study, we report low frequencies of CD3(+)NKp46(+) lymphocytes in blood, lymph nodes, and spleen, but increased frequencies in non-lymphatic organs, like liver and lung. Phenotypic analyses showed that the majority of CD3(+)NKp46(+) cells coexpressed the CD8αβ heterodimer, while a minor subset expressed the TCR-γδ, which was associated with a CD8αα(+) phenotype...
2016: Frontiers in Immunology
W W Li, P Sun, D D Chen, W Q Wang, G H Jiao, Y J Wang, L Zhou, B M Wang, J Zhang
OBJECTIVE: To investigate the preventive and therapeutic effects of rapamycin (RAPA) on autoimmune hepatitis and liver fibrosis induced by concanavalin A (ConA) and possible mechanisms. METHODS: Female C57BL/6 mice aged 8 weeks were randomly divided into normal control group, ConA model group, and ConA+RAPA treatment group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured; hematoxylin-eosin and Masson staining and Knodell HAI and Ishak scoring systems were used to evaluate the degrees of liver inflammation and fibrosis...
May 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Daila S Gridley, Michael J Pecaut
High-energy particle radiation could have a considerable impact on health during space missions. This study evaluated C57BL/6 mice on Day 40 after total-body (56)Fe(26+) irradiation at 0, 1, 2 and 3 gray (Gy). Radiation consistently increased thymus mass (one-way ANOVA: P < 0.005); spleen, liver and lung masses were similar among all groups. In the blood, there was no radiation effect on the white blood cell (WBC) count or major leukocyte types. However, the red blood cell count, hemoglobin, hematocrit and the CD8+ T cytotoxic (Tc) cell count and percentage all decreased, while both the CD4:CD8 (Th:Tc) cell ratio and spontaneous blastogenesis increased, in one or more irradiated groups compared with unirradiated controls (P < 0...
July 5, 2016: Journal of Radiation Research
Fang Zheng, Amanda Sparkes, Patrick De Baetselier, Steve Schoonooghe, Benoit Stijlemans, Serge Muyldermans, Véronique Flamand, Jo A Van Ginderachter, Nick Devoogdt, Geert Raes, Alain Beschin
PURPOSE: Kupffer cells (KCs), the liver resident macrophages, are important mediators of tissue homeostasis and pathogen clearance. However, depending on the inflammatory stimuli, KCs have been involved in divergent hepato-protective or hepato-destructive immune responses. The versatility of KCs in response to environmental triggers, in combination with the specific biomarkers they express, make these macrophages attractive in vivo targets for non-invasive monitoring of liver inflammation or pathogenicity...
June 23, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Tong Liu, Yujing Xia, Jingjing Li, Sainan Li, Jiao Feng, Liwei Wu, Rong Zhang, Shizan Xu, Keran Cheng, Yuqing Zhou, Shunfeng Zhou, Weiqi Dai, Kan Chen, Fan Wang, Jie Lu, Yingqun Zhou, Chuanyong Guo
OBJECTIVE: Shikonin possesses anti-inflammatory effects. However, its function in concanavalin A-induced acute liver injury remains uncertain. The aim of the present study was to investigate the functions of shikonin and its mechanism of protection on ConA-induced acute liver injury. MATERIALS AND METHODS: Balb/C mice were exposed to ConA (20 mg/kg) via tail vein injection to establish acute liver injury; shikonin (7.5 mg/kg and 12.5 mg/kg) was intraperitoneally administered 2 h before the ConA injection...
2016: Mediators of Inflammation
Katarzyna Byk, Krzysztof Jasinski, Zaneta Bartel, Agnieszka Jasztal, Barbara Sitek, Boguslaw Tomanek, Stefan Chlopicki, Tomasz Skorka
OBJECTIVE: To assess alterations in perfusion and liver function in the concanavalin A (ConA)-induced mouse model of acute liver failure (ALF) using two magnetic resonance imaging (MRI)-based methods: dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA contrast agent and arterial spin labelling (ASL). MATERIALS AND METHODS: BALB/c mice were studied using a 9.4 T MRI system. The IntraGateFLASH(TM) and FAIR-EPI pulse sequences were used for optimum mouse abdomen imaging...
May 9, 2016: Magma
Kan Chen, Jingjing Li, Sainan Li, Jiao Feng, Liwei Wu, Tong Liu, Rong Zhang, Shizan Xu, Keran Cheng, Yuqing Zhou, Shunfeng Zhou, Fan Wang, Weiqi Dai, Yujing Xia, Jie Lu, Yingqun Zhou, Chuanyong Guo
OBJECTIVE: In this study, we confirmed a protective effect of 15d-PGJ2 in concanavalin A (ConA)-induced fulminant hepatitis in mice and investigated the potential mechanism. MATERIALS AND METHODS: Balb/C mice were injected with ConA (25mg/kg) to induce acute fulminant hepatitis, and 15d-PGJ2 (2.5-10μg) was administered 30min after the ConA injection. The histological grade, pro-inflammatory cytokine and ROS levels, apoptosis and autophagy activity, the expression of HO-1, Nrf2, JNK and Bcl-2 activity were determined 2, 4, and 8h after the ConA injection...
May 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jingjing Li, Kan Chen, Sainan Li, Tong Liu, Fan Wang, Yujing Xia, Jie Lu, Yingqun Zhou, Chuanyong Guo
This study aimed to explore the effects of fucoidan from Fucus vesiculosus on concanavalin A (ConA)-induced acute liver injury in mice. Pretreatment with fucoidan protected liver function indicated by ALT, AST and histopathological changes by suppressing inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). In addition, intrinsic and extrinsic apoptosis mediated by Bax, Bid, Bcl-2, Bcl-xL and Caspase 3, 8, and 9 were inhibited by fucoidan and the action was associated with the TRADD/TRAF2 and JAK2/STAT1 signal pathways...
2016: PloS One
Raluca Wroblewski, Marietta Armaka, Vangelis Kondylis, Manolis Pasparakis, Henning Walczak, Hans-Willi Mittrücker, Christoph Schramm, Ansgar W Lohse, George Kollias, Hanno Ehlken
UNLABELLED: Death receptor (DR) ligands such as tumor necrosis factor (TNF) have been identified as fundamental mediators of liver damage both in mouse models and in humans. While the essential site of function of DR signaling is conceivably the hepatocyte, a systematic analysis is missing. Using mice with conditional gene ablation, we analyzed the tissue-specific function of DR signaling in T cell-dependent (concanavalin A) and independent (lipopolysaccharide/galactosamine) hepatitis and in models of bacterial infection (Listeria monocytogenes, lipopolysaccharide)...
August 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Yan Zhuang, Yi Li, Xuefeng Li, Qing Xie, Min Wu
Concanavalin A (ConA), a T-cell mitogen that induces acute autoimmune hepatitis, is widely used to model pathophysiological processes of human acute autoimmune liver disease. Although autophagy has been extensively studied in the past decade, little is known about its molecular mechanism underlying the regulation of ConA-induced acute hepatitis. In this study, we used a Cre-conditional atg7 KO mouse to investigate the effects of Atg7-associated autophagy on ConA-induced murine hepatitis. Our results demonstrated that atg7 deficiency in mice enhanced macrophage activation and increased pro-inflammatory cytokines upon ConA stimulation...
2016: PloS One
Sainan Li, Yujing Xia, Kan Chen, Jingjing Li, Tong Liu, Fan Wang, Jie Lu, Yingqun Zhou, Chuanyong Guo
BACKGROUND: Epigallocatechin-3-gallate (EGCG) is the most effective compound in green tea, and possesses a wide range of beneficial effects, including anti-inflammatory, antioxidant, antiobesity, and anticancer effects. In this study, we investigated the protective effects of EGCG in concanavalin A (ConA)-induced hepatitis in mice and explored the possible mechanisms involved in these effects. METHODS: Balb/C mice were injected with ConA (25 mg/kg) to induce acute autoimmune hepatitis, and EGCG (10 or 30 mg/kg) was administered orally twice daily for 10 days before ConA injection...
2016: Drug Design, Development and Therapy
Ya-Min Zhang, Zi-Rong Liu, Zi-Lin Cui, Chao Yang, Long Yang, Yang Li, Zhong-Yang Shen
AIM: To investigate the therapeutic effects and mechanisms of interleukin (IL)-22 in liver regeneration in mice with concanavalin A (ConA)-induced liver injury following 70% hepatectomy. METHODS: Mice were injected intravenously with ConA at 10 μg/g body weight 4 d before 70% hepatectomy to create a hepatitis model, and recombinant IL-22 was injected at 0.125 μg/g body weight 30 min prior to 70% hepatectomy to create a therapy model. Control animals received an intravenous injection of an identical volume of normal saline...
February 14, 2016: World Journal of Gastroenterology: WJG
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