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https://www.readbyqxmd.com/read/29649629/qingchangligan-formula-alleviates-acute-liver-injury-by-attenuating-extracellular-histone-associated-inflammation
#1
Lan Ding, Xiangying Zhang, Li Li, Chunyan Gou, Xiaolan Luo, Yang Yang, Tao Wen, Xiuhui Li
Qingchangligan formula (QCLGF) is a traditional Chinese medicine that has exhibited remarkable clinical efficacy for patients with acute-on-chronic liver failure (ACLF). However, the hepatoprotective mechanisms of QCLGF are not completely understood. Extracellular histones were recently identified as the novel inflammatory mediators involved in the pathogenesis of acute liver injury. This study aimed to investigate whether QCLGF provides hepatoprotection by targeting extracellular histones. We showed that QCLGF significantly improved the survival rate of the ConA-treated mice, ameliorated hepatotoxicity, and markedly decreased the levels of extracellular histones and the associated cytokines...
April 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29579707/arctigenin-protects-against-liver-injury-from-acute-hepatitis-by-suppressing-immune-cells-in-mice
#2
Xixi Cheng, Huafeng Wang, Jinlai Yang, Yingnan Cheng, Dan Wang, Fengrui Yang, Yan Li, Dongmei Zhou, Yanxia Wang, Zhenyi Xue, Lijuan Zhang, Qi Zhang, Luhong Yang, Rongxin Zhang, Yurong Da
As a phenylpropanoid and dibenzylbutyrolactone lignan present in medical plants, such as those used in traditional Chinese herbal medicine, including Arctium lappa (Niubang), arctigenin exhibits antimicrobial, anti-inflammatory, and anticancer activities. In this study, we investigated the protective role of arctigenin in Concanavalin A (ConA)-induced acute hepatitis in mice. Arctigenin remarkably reduced the congestion and necroinflammation of livers, and improved hepatic function (ALT and AST) in ConA-induced acute hepatitis in vivo...
March 23, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29448959/impaired-t-cell-mediated-hepatitis-in-peroxisome-proliferator-activated-receptor-alpha-ppar%C3%AE-deficient-mice
#3
Ian N Hines, Michael Kremer, Sherri M Moore, Michael D Wheeler
BACKGROUND: Peroxisome proliferator activated receptor alpha (PPARα), a regulator of enzymes involved in β oxidation, has been reported to influence lymphocyte activation. The purpose of this study was to determine whether PPARα plays a role in T cell-mediated hepatitis induced by Concanavalin A (ConA). METHODS: Wild type (wt) or PPARα-deficient (PPARα -/- ) mice were treated with ConA (15 mg/kg) by intravenous injection 0, 10 or 24 h prior to sacrifice and serum and tissue collection for analysis of tissue injury, cytokine response, T cell activation and characterization...
February 15, 2018: Biological Research
https://www.readbyqxmd.com/read/29428670/protective-effects-of-punica-granatum-pomegranate-peel-extract-on-concanavalin-a-induced-autoimmune-hepatitis-in-mice
#4
Tingting Wang, Ruoting Men, Mingxing Hu, Xiaoli Fan, Xiaoxue Yang, Xiaojun Huang, Tinghong Ye, Li Yang
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of an unknown etiology, glucocorticoid therapy is currently recognized as an effective treatment for AIH, but conventional application and patient compliance are both hindered by its side effects. The exploration of the AIH pathogenesis and the searching for the new candidate drugs that exert potential activity and low toxicity are urgently needed. Pomegranate peel extract (PoPx) is a natural extract of Punica granatum and has been reported to have anti-inflammatory and antioxidative properties...
February 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29421593/protective-effects-of-a-traditional-chinese-herbal-formula-jiang-xian-hugan-on-concanavalin-a-induced-mouse-hepatitis-via-nf-%C3%AE%C2%BAb-and-nrf2-signaling-pathways
#5
Huan-Huan Tang, Hai-Long Li, Yue-Xuan Li, Yan You, Yun-Yun Guan, Su-Lin Zhang, Li-Xin Liu, Wei-Lian Bao, Yong Zhou, Xiao-Yan Shen
ETHNOPHARMACOLOGICAL RELEVANCE: Jiang-Xian HuGan (JXHG) formulated by five natural products including Freshwater clam (Corbicula fluminea), Curcuma longa L., Ligustrum lucidum, Eclipta prostrata (L.) L. and Paeonia lactiflora Pall., has exhibited a great hepatoprotective effect. AIM OF THIS STUDY: We investigated the effect of JXHG on concanavalin A (ConA)-induced acute live injury in mice, and to elucidate its underlying molecular mechanisms. MATERIALS AND METHODS: Jiangkanling Capsule (900mg/kg), low-dose JXHG (LJXHG, 700mg/kg), high-dose JXHG (HJXHG, 1400mg/kg) were administered to mice by oral gavage daily for 20 days prior to a single intravenous injection of ConA (20mg/kg)...
February 5, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29420849/expression-of-microrna-155-in-inflammatory-cells-modulates-liver-injury
#6
Delia Blaya, Beatriz Aguilar-Bravo, Fengjie Hao, Silvia Casacuberta-Serra, Mar Coll, Luis Perea, Júlia Vallverdú, Isabel Graupera, Elisa Pose, Laura Llovet, Jordi Barquinero, Francisco Javier Cubero, Juan Caballería, Pere Ginès, Pau Sancho-Bru
miR-155 is involved in immune and inflammatory diseases and is associated with liver fibrosis and steatohepatitis. However, the mechanisms involved in miR-155 regulation of liver injury are largely unknown. The role of miR-155 in acute liver injury was assessed in wild type (WT), miR-155-/- and miR-155-/- mice transplanted with WT bone marrow. Additionally, miR-155 expression was evaluated in liver tissue and peripheral blood mononuclear cells (PBMC) of patients with autoimmune hepatitis. Concanavalin A (ConA) but not acetaminophen (APAP) treatment increased the expression of miR-155 in liver tissue of WT mice...
February 8, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29409050/shp-deficiency-increases-inflammatory-liver-injury-through-cxcl2-driven-neutrophil-recruitment-in-mice
#7
Jung-Ran Noh, Yong-Hoon Kim, Don-Kyu Kim, Jung Hwan Hwang, Kyoung-Shim Kim, Dong-Hee Choi, Seon-Jin Lee, Hee Gu Lee, Tae Geol Lee, Hong-Lei Weng, Steven Dooley, Hueng-Sik Choi, Chul-Ho Lee
Although detailed pathophysiological mechanisms of fulminant hepatitis remain elusive, immune cell recruitment with excessive cytokine production is a well-recognized hallmark of the disease. We determined the function of orphan nuclear receptor small heterodimer partner (SHP) in concanavalin A (ConA)-induced hepatitis model. Male C57BL/6J mice were injected intravenously with either a lethal dose (25 mg/kg) or a sub-lethal dose (15 mg/kg) of ConA. For the C-X-C motif chemokine ligand (CXCL) 2 neutralization study, mice were intravenously administered anti-mouse CXCL2 antibody (100 μg/mouse)...
February 2, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29407573/identification-of-duck-il-4-and-its-inhibitory-effect-on-il-17a-expression-in-r-anatipestifer-stimulated-splenic-lymphocytes
#8
Cherry P Fernandez, Fahmida Afrin, Rochelle A Flores, Woo H Kim, Jipseol Jeong, Suk Kim, Hyun S Lillehoj, Wongi Min
As the dysregulation of IL-17 is implicated in the pathogenesis of various autoimmune and inflammatory diseases, the suppression of IL-17 production by Th2 cytokines could alleviate the development of these diseases. Previously, we confirmed that inflammatory cytokines including IL-17A are strongly associated with R. anatipestifer infection, which is one of the most important bacterial pathogens in the duck industry. Here, we found that IL-4 treatment downregulated the expression of IL-17A and IL-17F transcripts in splenic lymphocytes stimulated with R...
February 2, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29377208/ceacam1-controls-il-2-dependent-regulatory-t-cell-induction-in-immune-mediated-hepatitis
#9
Andrea Kristina Horst, Claudia Wegscheid, Christoph Schaefers, Birgit Schiller, Katrin Neumann, Sebastian Lunemann, Annika E Langeneckert, Karl J Oldhafer, Christina Weiler-Normann, Karl S Lang, Bernhard B Singer, Marcus Altfeld, Linda Diehl, Gisa Tiegs
A dysbalance between effector T cells (Tconv) and regulatory T cells (Tregs) and impaired Tregs function can cause autoimmune liver disease. Therefore, it is important to identify molecular mechanisms that control Treg homeostasis. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is an immune co-receptor with dichotomous roles in T cell regulation: its short isoform (CEACAM1S) can activate T cells and induce Tregs, whereas its long isoform (CEACAM1L) containing two intracellular immune receptor tyrosine-based inhibitory motifs (ITIMs), can inhibit activated T cell function...
January 29, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29220536/cd36-deficiency-attenuates-immune-mediated-hepatitis-in-mice-by-modulating-the-proapoptotic-effects-of-cxc-chemokine-ligand-10
#10
Che Xu, Chen Zhang, Jie Ji, Chao Wang, Jing Yang, Biao Geng, Ting Zhao, Hong Zhou, Xianmin Mu, Jinshun Pan, Shi Hu, Yuanfang Lv, Xingguo Chen, Hao Wen, Qiang You
The scavenger receptor CD36 recognizes a diverse set of ligands and has been implicated in a wide variety of normal and pathological processes, including lipid metabolism, angiogenesis, atherosclerosis, and phagocytosis. In particular, recent findings have demonstrated its crucial functions in sterile inflammation and tumor metastasis. However, the role of CD36 in immune-mediated hepatitis remains unclear. Concanavalin A (ConA)-induced liver injury is a well-established experimental T cell-mediated hepatitis...
December 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29174851/hepatoprotective-effect-of-quercetin-via-traf6-jnk-pathway-in-acute-hepatitis
#11
Liwei Wu, Chengfen Wang, Jingjing Li, Sainan Li, Jiao Feng, Tong Liu, Shizan Xu, Wenwen Wang, Xiya Lu, Kan Chen, Yujing Xia, Xiaoming Fan, Chuanyong Guo
Quercetin, as a member of the flavonoids family, has many beneficial properties. The aim of our study was to evaluate the protective effect of quercetin in ConA-induced hepatitis in mice, and to clarify its mechanism of action. Hepatitis was induced by using ConA (25 mg/kg), and quercetin was administered intragastrically at the dose of 100 mg/kg or 200 mg/kg for 5 days before ConA injection. The serum levels of liver enzymes, inflammatory cytokines and other marker proteins were determined at 2 h, 8 h and 24 h after ConA injection...
December 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29149046/impact-of-a-single-oral-acute-dose-of-aflatoxin-b%C3%A2-on-liver-function-cytokines-and-the-lymphoproliferative-response-in-c57bl-6-mice
#12
Angélica Tieme Ishikawa, Elisa Yoko Hirooka, Paula Leonello Alvares E Silva, Ana Paula Frederico Rodrigues Loureiro Bracarense, Karina Keller Marques da Costa Flaiban, Claudia Yuri Akagi, Osamu Kawamura, Marcio Carvalho da Costa, Eiko Nakagawa Itano
Aflatoxin B₁ (AFB₁), a mycotoxin found in food and feed, exerts harmful effects on humans and animals. The liver is the earliest target of AFB₁, and its effects have been evaluated in animal models exposed to acute or chronic doses. Considering the possibility of sporadic ingestion of AFB₁-contaminated food, this study investigated the impact of a single oral dose of AFB₁ on liver function/cytokines and the lymphoproliferative response in mice. C57BL/6 mice were treated with a single oral AFB₁ dose (44, 442 or 663 μg AFB₁/kg of body weight) on the first day...
November 17, 2017: Toxins
https://www.readbyqxmd.com/read/29111266/hepatoprotective-and-inhibiting-hbv-effects-of-polysaccharides-from-roots-of-sophora-flavescens
#13
Hua Yang, Zhenhua Zhou, Lifang He, Hao Ma, Wensheng Qu, Jiye Yin, Mengfan Jia, Xiunan Zhao, Junjie Shan, Yueqiu Gao
Roots of Sophora flavescens is an important herbal medicine for treatment of HBV and hepatic carcinoma in China. Alkaloids in the root were well known for exhibiting good hepato-protective and anti-HBV effects. However, polysaccharides as main components in the root remained unknown. In the studies, we investigated the chemical features and hepatoprotective effects of Sophora flavescens polysaccharides (SFP-100 and its active fractions) with ConA-induced hepatitis mice, human liver LO2 cells and HepG2.2.15 cells...
October 27, 2017: International Journal of Biological Macromolecules
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
#14
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...
May 2018: 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
#15
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-harbors-immune-inhibitory-inflammatory-cells
#16
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 10-20% of u-ADSCs expressed the CD45 leukocyte-related antigen...
December 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
#17
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
#18
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 part 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...
October 24, 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
#19
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
#20
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 natural killer T (iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs, such as the 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...
November 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
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