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https://www.readbyqxmd.com/read/28330461/impaired-liver-regeneration-is-associated-with-reduced-cyclin-b1-in-natural-killer-t-cell-deficient-mice
#1
Ami Ben Ya'acov, Hadar Meir, Lydia Zolotaryova, Yaron Ilan, Eyal Shteyer
BACKGROUND: It has been shown that the proportion of natural killer T cells is markedly elevated during liver regeneration and their activation under different conditions can modulate this process. As natural killer T cells and liver injury are central in liver regeneration, elucidating their role is important. METHODS: The aim of the current study is to explore the role of natural killer T cells in impaired liver regeneration. Concanvalin A was injected 4 days before partial hepatectomy to natural killer T cells- deficient mice or to anti CD1d1-treated mice...
March 23, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28261494/radioprotective-effects-of-cimetidine-on-rats-irradiated-by-long-term-low-dose-rate-neutrons-and-60-co-%C3%AE-rays
#2
Ding-Wen Jiang, Qing-Rong Wang, Xian-Rong Shen, Ying He, Tian-Tian Qian, Qiong Liu, Deng-Yong Hou, Yu-Ming Liu, Wei Chen, Xin Ren, Ke-Xian Li
BACKGROUND: Cimetidine, an antagonist of histamine type II receptors, has shown protective effects against γ-rays or neutrons. However, there have been no reports on the effects of cimetidine against neutrons combined with γ-rays. This study was carried out to evaluate the protective effects of cimetidine on rats exposed to long-term, low-dose-rate neutron and γ-ray combined irradiation (n-γ LDR). METHODS: Fifty male Sprague-Dawley (SD) rats were randomly divided into 5 groups: the normal control group, radiation model group, 20 mg/(kg · d) cimetidine group, 80 mg/(kg · d) cimetidine group and 160 mg/(kg · d) cimetidine group (10 rats per group)...
2017: Military Medical Research
https://www.readbyqxmd.com/read/28246592/stellate-cell-activation-and-imbalanced-expression-of-tgf-%C3%AE-1-tgf-%C3%AE-3-in-acute-autoimmune-liver-lesions-induced-by-cona-in-mice
#3
Liyun Wang, Lei Tu, Jinping Zhang, Keshu Xu, Wei Qian
Objective. To study the pathogenic feature of liver injury, activation of hepatic stellate cells, and dynamic expression of TGF-β1/TGF-β3 to reveal their role in liver injury induced by ConA. Methods. Mice were randomly divided into control group and ConA treatment group. ConA (20 mg/kg) was injected through vena caudalis in ConA treatment group; the controls received the same volume of saline injection. After injection for 2 h, 8 h, 24 h, and 48 h, animals were terminated. Blood, liver, and spleen were harvested...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28174672/immunomodulatory-effects-of-adipose-tissue-derived-stem-cells-on-concanavalin-a-induced-acute-liver-injury-in-mice
#4
Yasuma Yoshizumi, Hiroshi Yukawa, Ryoji Iwaki, Sanae Fujinaka, Ayano Kanou, Yuki Kanou, Tatsuya Yamada, Shingo Nakagawa, Tomomi Ohara, Kenta Nakagiri, Yusuke Ogihara, Yoko Tsutsui, Yumi Hayashi, Masatoshi Ishigami, Yoshinobu Baba, Tetsuya Ishikawa
Cell therapy with adipose tissue-derived stem cells (ASCs) is expected to be a candidate for the treatment of fulminant hepatic failure (FHF), which is caused by excessive immune responses. In order to evaluate the therapeutic effects of ASCs on FHF, the in vitro and in vivo immunomodulatory effects of ASCs were examined in detail in the mouse model. The in vitro effects of ASCs were examined by assessing their influence on the proliferation of lymphomononuclear cells (LMCs) stimulated with three kinds of mitogens: phorbol 12-myristate 13-acetate (PMA) plus ionomycin, concanavalin A (ConA), and lipopolysaccharide (LPS)...
January 8, 2017: Cell Medicine
https://www.readbyqxmd.com/read/28109817/salecan-protected-against-concanavalin-a-induced-acute-liver-injury-by-modulating-t-cell-immune-responses-and-nmr-based-metabolic-profiles
#5
Qi Sun, Xi Xu, Xiao Yang, Dan Weng, Junsong Wang, Jianfa Zhang
Salecan, a water-soluble extracellular β-glucan produced by Agrobacterium sp. ZX09, has been reported to exhibit a wide range of biological effects. The aims of the present study were to investigate the protective effect of salecan against Concanavalin A (ConA)-induced hepatitis, a well-established animal model of immune-mediated liver injury, and to search for possible mechanisms. C57BL/6 mice were pretreated with salecan followed by ConA injection. Salecan treatment significantly reduced ConA-induced acute liver injury, and suppressed the expression and secretion of inflammatory cytokines including interferon (IFN)-γ, interleukin (IL)-6 and IL-1β in ConA-induced liver injury model...
January 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28092402/%C3%AE-%C3%AE-t-cells-are-indispensable-for-interleukin-23-mediated-protection-against-concanavalin-a-induced-hepatitis-in-hepatitis-b-virus-transgenic-mice
#6
Ziyu Meng, Jingya Wang, Yifang Yuan, Guangchao Cao, Shuobing Fan, Chao Gao, Li Wang, Zheng Li, Xiaoli Wu, Zhenzhou Wu, Liqing Zhao, Zhinan Yin
Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδ T cells and liver damage in patients with hepatitis B virus (HBV). However, whether γδ T cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using HBV transgenic (HBs-Tg) and HBs-Tg T-cell receptor-δ-deficient (TCR-δ(-/-) ) mice, we found that mice genetically deficient in γδ T cells exhibited more severe liver damage upon Concanavalin A (Con A) treatment, as indicated by substantially higher serum alanine aminotransferase levels, further elevated interferon-γ (IFN-γ) levels and more extensive necrosis...
January 16, 2017: Immunology
https://www.readbyqxmd.com/read/28065940/cd24-aggravates-acute-liver-injury-in-autoimmune-hepatitis-by-promoting-ifn-%C3%AE-production-by-cd4-t-cells
#7
Chenhong Zheng, Shulei Yin, Yang Yang, Yizhi Yu, Xiaohua Xie
The T-cell-mediated immune response is implicated in many clinical hepatic injuries, such as autoimmune hepatitis and acute virus hepatitis. CD24 is widely expressed by different immune cells and plays an important role in the pathogenesis of many autoimmune diseases. However, the role of CD24 in T-cell-mediated liver injury has not been elucidated until now. Here we showed that CD24 deficiency protects mice from concanavalin A (ConA)-induced fulminant liver injury by reducing serum interferon-γ (IFN-γ) levels...
January 9, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28032440/magnolol-attenuates-concanavalin-a-induced-hepatic-fibrosis-inhibits-cd4-t-helper-17-th17-cell-differentiation-and-suppresses-hepatic-stellate-cell-activation-blockade-of-smad3-smad4-signalling
#8
Hongjun Zhang, Baoling Ju, Xiaoli Zhang, Yanfei Zhu, Ying Nie, Yuanhong Xu, Qiuxia Lei
Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis, which displays anti-inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune-related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo...
December 29, 2016: Basic & Clinical Pharmacology & Toxicology
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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)...
April 2017: Gut
https://www.readbyqxmd.com/read/27537353/anti-tumor-effects-of-the-polysaccharide-isolated-from-tarphochlamys-affinis-in-h22-tumor-bearing-mice
#17
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
#18
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
#19
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
#20
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
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