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ConA liver

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https://www.readbyqxmd.com/read/29034470/involvement-of-the-nrf2-ho-1-co-axis-and-therapeutic-intervention-with-the-co-releasing-molecule-corm-a1-in-a-murine-model-of-autoimmune-hepatitis
#1
Katia Mangano, Eugenio Cavalli, Santa Mammana, Maria Sofia Basile, Rosario Caltabiano, Antonio Pesce, Stefano Puleo, Atanas G Atanasov, Gaetano Magro, Ferdinando Nicoletti, Paolo Fagone
Concanavalin A (ConA)-induced hepatitis is an experimental model of human autoimmune hepatitis induced in rodents by i.v. injection of Con A. The disease is characterized by increase in serum levels of transaminases and massive immune infiltration of the livers. Type 1, type 2 and type 17 cytokines play a pathogenic role in the development of ConA-induced hepatitis. To understand further the immunoregulatory mechanisms operating in the development and regulation of ConA-induced hepatitis, we have evaluated the role of the anti-inflammatory pathway Nrf2/HO-1/CO (Nuclear Factor E2-related Factor 2/Heme Oxygenase-1/Carbon Monoxide) in this condition and determined whether the in vivo administration of CO via the CO-releasing molecule (CORM) CORM-A1, influences serological and histological development of Con-A-induced hepatitis...
October 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29023933/mir-15a-16-1-suppresses-ahr-dependent-il-22-secretion-in-cd4-t-cells-and-contributes-to-immune-mediated-organ-injury
#2
Zhou Lu, Jiajing Liu, Xiaoming Liu, Enyu Huang, Jiao Yang, Jiawen Qian, Dan Zhang, Ronghua Liu, Yiwei Chu
Interleukin-22 (IL-22), as a link between leukocytic and non-leukocytic cells, has gained increasing attention for its pronounced tissue-protective properties. MicroRNAs (miRNAs), emerging as crucial immune modulators, have been reported to be involved in the production and action of various cytokines. However, the precise control of IL-22 by miRNAs and its subsequent actions remained to be elucidated. In this study, we found a negative correlation between the expression of miR-15a/16-1 and IL-22 in the model of concanavalinA (ConA)-induced immune-mediated liver injury...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28891216/the-cd45-fraction-in-murine-adipose-tissue-derived-stromal-cells-harbor-immune-inhibitory-inflammatory-cells
#3
Alessandro Nasti, Yoshio Sakai, Akihiro Seki, Geraldine Belen Buffa, Takuya Komura, Hatsune Mochida, Masatoshi Yamato, Keiko Yoshida, Tuyen T B Ho, Masayuki Takamura, Soichiro Usui, Takashi Wada, Masao Honda, Shuichi Kaneko
Stromal cells in adipose tissue are useful for repair/regenerative therapy as they harbor a substantial number of mesenchymal stem cells; therefore, freshly isolated autologous uncultured adipose tissue-derived stromal cells (u-ADSCs) are useful for regenerative therapy, and obviate the need for mesenchymal stem cells. We evaluated the therapeutic effect of murine u-ADSCs and sorted subsets of u-ADSCs in a concanavalin A (ConA)-induced murine model of hepatitis, as well as their characteristics. We found that 10% to 20% of u-ADSCs expressed the CD45 leukocyte-related antigen...
September 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28881722/hepatic-nk-cell-mediated-hypersensitivity-to-cona-induced-liver-injury-in-mouse-liver-expressing-hepatitis-c-virus-polyprotein
#4
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 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28829572/immunomodulatory-therapy-of-inflammatory-liver-disease-using-selectin-binding-glycopolymers
#5
Matthias Bartneck, Christopher Thorsten Schlößer, Matthias Barz, Rudolf Zentel, Christian Trautwein, Twan Lammers, Frank Tacke
Immunotherapies have the potential to significantly advance treatment of inflammatory disease and cancer, which are in large parts driven by immune cells. Selectins control the first step in immune cell adhesion and extravasation, thereby guiding leukocyte trafficking to tissue lesions. We analyzed four different highly specific selectin-binding glycopolymers, based on linear poly(2-hydroxypropyl)-methacrylamide (PHPMA) polymers. These glycopolymers contain either the tetrasaccharide sialyl-Lewis(X) (SLe(X)), or the individual carbohydrates fucose, galactose, and sialic acids mimicking the complex SLe(X) binding motive...
August 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/28804705/possible-involvement-of-liver-resident-macrophages-kupffer-cells-in-the-pathogenesis-of-both-intrahepatic-and-extrahepatic-inflammation
#6
Yuki Kakinuma, Takuya Kimura, Yoshifumi Watanabe
Liver resident macrophages designated Kupffer cells (KCs) form the largest subpopulation of tissue macrophages. KCs are involved in the pathogenesis of liver inflammation. However, the role of KCs in the systemic inflammation is still elusive. In this study, we examined whether KCs are involved in not only intrahepatic inflammation but also extrahepatic systemic inflammation. Administration of clodronate liposomes resulted in the KC deletion and in the suppression of liver injury in T cell-mediated hepatitis by ConA as a local acute inflammation model, while the treatment did not influence dextran sulfate sodium- (DSS-) induced colitis featured by weight loss, intestinal shrink, and pathological observation as an ectopic local acute inflammation model...
2017: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28751426/parp2-deficiency-affects-invariant-nkt-cell-maturation-and-protects-mice-from-concanavalin-a-induced-liver-injury
#7
Aveline Filliol, Claire Piquet-Pellorce, Sarah Dion, Valentine Genet, Catherine Lucas-Clerc, Françoise Dantzer, Michel Samson
Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during Concanavalin A (ConA)-induced hepatitis. In this mice model, ConA activates immune cells which promote inflammation and induce hepatocyte death, mediated by the activated invariant NKT-(iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs such as spleen, thymus, and bone marrow in Parp2 deficient mice to better define the role of PARP proteins in liver immunity and inflammation at steady state and during ConA-induced hepatitis...
July 27, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28710903/stellate-cells-orchestrate-concanavalin-a-induced-acute-liver-damage
#8
Richa Rani, Ashish Tandon, Jiang Wang, Sudhir Kumar, Chandrashekhar R Gandhi
Concanavalin A (ConA) causes immune cell-mediated liver damage, but the contribution of resident nonparenchymal cells (NPCs) is also evident. Hepatic stellate cells (HSCs) induce hepatic inflammation and immunological reactions; we therefore investigated their role in ConA-induced liver injury. ConA was administered i.v. to control or HSC-depleted mice; hepatic histopathology and cytokines/chemokines were determined after 6 hours. In vitro, effects of ConA-conditioned HSC medium on hepatocytes were determined...
September 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28603092/crosstalk-of-liver-immune-cells-and-cell-death-mechanisms-in-different-murine-models-of-liver-injury-and-its-clinical-relevance
#9
Hilal Ahmad Khan, Muhammad Zishan Ahmad, Junaid Ali Khan, Muhammad Imran Arshad
BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions...
June 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/28534962/galectin%C3%A2-9-ameliorates-fulminant-liver-injury
#10
Tomoko Tadokoro, Asahiro Morishita, Teppei Sakamoto, Shintaro Fujihara, Koji Fujita, Shima Mimura, Kyoko Oura, Takako Nomura, Joji Tani, Hirohito Yoneyama, Hisakazu Iwama, Takashi Himoto, Toshiro Niki, Mitsuomi Hirashima, Tsutomu Masaki
Fulminant hepatitis is a severe liver disease resulting in hepatocyte necrosis. Galectin‑9 (Gal‑9) is a tandem‑repeat‑type galectin that has been evaluated as a potential therapeutic agent for various diseases that regulate the host immune system. Concanavalin A (ConA) injection into mice results in serious, immune‑mediated liver injury similar to human viral, autoimmune and fulminant hepatitis. The present study investigated the effects of Gal‑9 treatment on fulminant hepatitis in vivo and the effect on the expression of microRNAs (miRNAs), in order to identify specific miRNAs associated with the immune effects of Gal‑9...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28526886/fk866-attenuates-acute-hepatic-failure-through-c-jun-n-terminal-kinase-jnk-dependent-autophagy
#11
Enshuang Guo, Renlong Li, Jiankun Yang, Jun Zhang, Anyi Li, Yan Yang, Shenpei Liu, Anding Liu, Xiaojing Jiang
FK866 exhibits a protective effect on D-galactosamine (GaIN)/lipopolysaccharide (LPS) and concanavalin A (ConA)-induced acute liver failure (ALF), but the mechanism by which FK866 affords this benefit has not yet been elucidated. Autophagy has a protective effect on acute liver injury. However, the contribution of autophagy to FK866-conferred hepatoprotection is still unclear. This study aimed to investigate whether FK866 could attenuate GaIN/LPS and ConA-induced ALF through c-jun-N-terminal kinase (JNK)-dependent autophagy...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28488390/mesenchymal-stem-cells-protect-from-acute-liver-injury-by-attenuating-hepatotoxicity-of-liver-nkt-cells-in-inos-and-ido-dependent-manner
#12
Marina Gazdic, Bojana Simovic Markovic, Ljubica Vucicevic, Tamara Nikolic, Valentin Djonov, Nebojsa Arsenijevic, Vladimir Trajkovic, Miodrag L Lukic, Vladislav Volarevic
The effects of mesenchymal stem cells (MSCs) on phenotype and function of natural killer T (NKT) cells, is not understood. We used concanavalin A (ConA) - and α-galactosylceramide (α-GalCer)-induced liver injury to evaluate effects of MSCs on NKT-dependent hepatotoxicity. Mouse MSCs (mMSCs) significantly reduced Con A- and α-GalCer-mediated hepatitis in C57Bl/6 mice, as demonstrated by histopathological and biochemical analysis, attenuated influx of inflammatory (T-bet(+) TNF-α, IFN-γ producing and GATA3(+) , IL-4-producing) liver NKT cells and down-regulated TNF-α, IFN-γ and IL-4 levels in the sera...
May 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28482408/-protective-effect-of-intraperitoneal-transplantation-of-human-liver-derived-stem-cells-at-different-times-against-concanavalin-a-induced-acute-liver-injury-in-mice
#13
Y Z Bi, Z Fan, D F Chen, S S Li, Q Y Wang, P F Gao, Q Q Wang, Z P Duan, Y Chen, L B Kong, Y B Wang, F Hong
Objective: To investigate the protective effect of intraperitoneal transplantation of human liver-derived stem cells at different times against concanavalin A (ConA)-induced acute liver injury in mice. Methods: A total of 88 male C57BL/6 mice were randomly divided into normal control group (group C), ConA model group (group M), and human liver-derived stem cells (HYX1)+ConA group (group E); according to the interval between phosphate buffer/HYX1 injection and ConA injection, Groups M and E were further divided into 3-hour groups (M1 and E1 groups), 6-hour groups (M2 and E2 groups), 12-hour groups (M3 and E3 groups), 24-hour groups (M4 and E4 groups), and 48-hour groups (M5 and E5 groups)...
March 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28450923/expression-and-roles-of-tipe2-in-autoimmune-hepatitis
#14
Jinhua Qian, Zongde Meng, Jiachang Guan, Zhiwei Zhang, Yangang Wang
Tumor necrosis factor, alpha-induced protein 8-like 2 (TIPE2) is associated with the development of hepatic inflammatory diseases. However, to date, the possible role of TIPE2 in autoimmune hepatitis (AIH) has not been reported. The present study aimed to investigate the expression of TIPE2 in peripheral blood mononuclear cells (PBMCs) of mice with AIH. Furthermore, the liver function, pro-inflammatory cytokine production and hepatic histopathology were examined in TIPE2-deficient mice in order to evaluate whether TIPE2 is involved in the pathogenesis of AIH...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28416868/a-synergistic-effect-of-cremophor-and-beta-glucosylceramide-to-exert-liver-and-sugar-protection
#15
Yehudit Shabat, Yaron Ilan
Many commonly used drugs carry the potential to induce hepatotoxicity, and a large number of foods and beverages induce an increase in blood sugar levels. A change in lifestyle by omitting these compounds is not applicable in many circumstances. β-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an effect on the immune system. Cremophor EL (CrEL) is a synthetic, nonionic surfactant that is used as a vehicle for the administration of water-insoluble compounds. The aim of the present study was to determine the synergistic effect of oral administration of the combination of GC and CrEL (GCC) when added to potential toxic substrates or to sugar-enriched compounds...
April 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28377718/sophocarpine-protects-mice-from-cona-induced-hepatitis-via-inhibition-of-the-ifn-gamma-stat1-pathway
#16
Xiu-Xiu Sang, Rui-Lin Wang, Cong-En Zhang, Shi-Jing Liu, Hong-Hui Shen, Yu-Ming Guo, Ya-Ming Zhang, Ming Niu, Jia-Bo Wang, Zhao-Fang Bai, Xiao-He Xiao
Sophocarpine is the major pharmacologically active compound of the traditional Chinese herbal medicine Radix Sophorae Subprostratae which has been used in treating hepatitis for years in China. It has been demonstrated that Sophocarpine exerts an activity in immune modulation and significantly decreases the production of inflammatory cytokines. However, the protective effects of Sophocarpine in T cell-dependent immune hepatitis remained unknown. The aim of this study was to determine the protective effects and pharmacological mechanisms of Sophocarpine on Concanavalin A (ConA)-induced hepatitis, an experimental model of T cell-mediated liver injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28330461/impaired-liver-regeneration-is-associated-with-reduced-cyclin-b1-in-natural-killer-t-cell-deficient-mice
#17
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
#18
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
#19
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
#20
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
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