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https://www.readbyqxmd.com/read/27832933/a-plant-cell-expressed-recombinant-anti-tnf-fusion-protein-is-biologically-active-in-the-gut-and-alleviates-immune-mediated-hepatitis-and-colitis
#1
Yaron Ilan, Svetlana Gingis-Velitski, Ami Ben Ya'aco, Yehudit Shabbat, Lidya Zolotarov, Einat Almon, Yoseph Shaaltiel
: The orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) (n=6) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human antibody IgG1 domain. AIM: To evaluate the immune modulatory effect of the oral administration of plant cells expressing PRX-106. METHODS: Mice treated with Concanavalin A (ConA) to induce immune hepatitis was orally treated with cells expressing PRX-106 containing 0...
November 4, 2016: Immunobiology
https://www.readbyqxmd.com/read/27831558/ripk1-protects-from-tnf-%C3%AE-mediated-liver-damage-during-hepatitis
#2
Aveline Filliol, Claire Piquet-Pellorce, Jacques Le Seyec, Muhammad Farooq, Valentine Genet, Catherine Lucas-Clerc, John Bertin, Peter J Gough, Marie-Thérèse Dimanche-Boitrel, Peter Vandenabeele, Mathieu Jm Bertrand, Michel Samson
Cell death of hepatocytes is a prominent characteristic in the pathogenesis of liver disease, while hepatolysis is a starting point of inflammation in hepatitis and loss of hepatic function. However, the precise molecular mechanisms of hepatocyte cell death, the role of the cytokines of hepatic microenvironment and the involvement of intracellular kinases, remain unclear. Tumor necrosis factor alpha (TNF-α) is a key cytokine involved in cell death or survival pathways and the role of RIPK1 has been associated to the TNF-α-dependent signaling pathway...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27821872/enterogenous-bacterial-glycolipids-are-required-for-the-generation-of-natural-killer-t-cells-mediated-liver-injury
#3
Yingfeng Wei, Benhua Zeng, Jianing Chen, Guangying Cui, Chong Lu, Wei Wu, Jiezuan Yang, Hong Wei, Rufeng Xue, Li Bai, Zhi Chen, Lanjuan Li, Kazuya Iwabuchi, Toshimitsu Uede, Luc Van Kaer, Hongyan Diao
Glycolipids are potent activator of natural killer T (NKT) cells. The relationship between NKT cells and intestinal bacterial glycolipids in liver disorders remained unclear. We found that, in sharp contrast to specific pathogen-free (SPF) mice, germ-free (GF) mice are resistant to Concanavalin A (ConA)-induced liver injury. ConA treatment failed to trigger the activation of hepatic NKT cells in GF mice. These defects correlated with the sharply reduced levels of CD1d-presented glycolipid antigens in ConA-treated GF mice compared with SPF counterparts...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27760053/a-murder-mystery-in-the-liver-who-done-it-and-how
#4
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...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27714757/the-protective-effect-of-the-natural-compound-hesperetin-against-fulminant-hepatitis-in-vivo-and-in-vitro
#5
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...
January 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27685635/circulating-histones-are-major-mediators-of-systemic-inflammation-and-cellular-injury-in-patients-with-acute-liver-failure
#6
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
https://www.readbyqxmd.com/read/27639182/effects-of-kinsenoside-a-potential-immunosuppressive-drug-for-autoimmune-hepatitis-on-dendritic-cells-cd8-t-cells-communication-in-mice
#7
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 proinflammatory cytokines, in concanavalin A-induced T-cell-mediated hepatitis, and in dendritic cells (DCs) 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 cell 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
https://www.readbyqxmd.com/read/27566130/pgam5-mediated-programmed-necrosis-of-hepatocytes-drives-acute-liver-injury
#8
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
https://www.readbyqxmd.com/read/27537353/anti-tumor-effects-of-the-polysaccharide-isolated-from-tarphochlamys-affinis-in-h22-tumor-bearing-mice
#9
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
https://www.readbyqxmd.com/read/27527854/hepatic-nk-cell-mediated-hypersensitivity-to-cona-induced-liver-injury-in-mouse-liver-expressing-hepatitis-c-virus-polyprotein
#10
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
https://www.readbyqxmd.com/read/27524863/protective-effects-of-dracocephalum-heterophyllum-in-cona-induced-acute-hepatitis
#11
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
https://www.readbyqxmd.com/read/27471504/porcine-cd3-nkp46-lymphocytes-have-nk-cell-characteristics-and-are-present-in-increased-frequencies-in-the-lungs-of-influenza-infected-animals
#12
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
https://www.readbyqxmd.com/read/27470891/-preventive-and-therapeutic-effects-of-rapamycin-against-autoimmune-hepatitis-and-liver-fibrosis-and-possible-mechanisms
#13
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
https://www.readbyqxmd.com/read/27380804/changes-in-the-distribution-and-function-of-leukocytes-after-whole-body-iron-ion-irradiation
#14
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
https://www.readbyqxmd.com/read/27339464/molecular-imaging-with-kupffer-cell-targeting-nanobodies-for-diagnosis-and-prognosis-in-mouse-models-of-liver-pathogenesis
#15
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
https://www.readbyqxmd.com/read/27293314/shikonin-attenuates-concanavalin-a-induced-acute-liver-injury-in-mice-via-inhibition-of-the-jnk-pathway
#16
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
https://www.readbyqxmd.com/read/27160299/mri-based-assessment-of-liver-perfusion-and-hepatocyte-injury-in-the-murine-model-of-acute-hepatitis
#17
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
https://www.readbyqxmd.com/read/27133055/15d-pgj2-alleviates-cona-induced-acute-liver-injury-in-mice-by-up-regulating-ho-1-and-reducing-hepatic-cell-autophagy
#18
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
https://www.readbyqxmd.com/read/27035150/pretreatment-with-fucoidan-from-fucus-vesiculosus-protected-against-cona-induced-acute-liver-injury-by-inhibiting-both-intrinsic-and-extrinsic-apoptosis
#19
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
https://www.readbyqxmd.com/read/26991125/opposing-role-of-tumor-necrosis-factor-receptor-1-signaling-in-t-cell-mediated-hepatitis-and-bacterial-infection-in-mice
#20
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
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