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Xuehua Piao, Soh Yamazaki, Sachiko Komazawa-Sakon, Sanae Miyake, Osamu Nakabayashi, Takeyuki Kurosawa, Tetsuo Mikami, Minoru Tanaka, Nico Van Rooijen, Masaki Ohmuraya, Akira Oikawa, Yuko Kojima, Soichiro Kakuta, Yasuo Uchiyama, Masato Tanaka, Hiroyasu Nakano
: Tissue-resident macrophages and bone marrow (BM)-derived monocytes play a crucial role in the maintenance of tissue homeostasis; however, their contribution to recovery from acute tissue injury is not fully understood. To address this issue, we generated an acute murine liver injury model using hepatocyte-specific Cflar-deficient (Cflar(Hep-low) ) mice. Cellular FLICE-inhibitory protein (cFLIP) expression was downregulated in Cflar-deficient hepatocytes, which thereby increased susceptibility of hepatocytes to death receptor-induced apoptosis...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Carsten Deppermann, Paul Kubes
The primary function of platelets is to patrol the vasculature and seal vessel breaches to limit blood loss. However, it is becoming increasingly clear that they also contribute to pathophysiological conditions like thrombosis, atherosclerosis, stroke and infection. Severe sepsis is a devastating disease that claims hundreds of thousands of lives every year in North America and is a major burden to the public health system. Platelet surface receptors like GPIb, αIIbβ3, TLR2 and TLR4 are involved in direct platelet-bacteria interactions...
October 18, 2016: Seminars in Immunology
Takayuki Koga, Pei-Li Yao, Maryam Goudarzi, Iain A Murray, Gayathri Balandaram, Frank J Gonzalez, Gary H Perdew, Albert J Fornace, Jeffrey M Peters
Alcoholic liver disease is a pathological condition caused by over-consumption of alcohol. Due to the high morbidity and mortality associated with this disease, there remains a need to elucidate the molecular mechanisms underlying its etiology and to develop new treatments. Since peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) modulates ethanol-induced hepatic effects, the present study examined alterations in gene expression that may contribute to this disease. Chronic ethanol treatment causes increased hepatic CYP2B10 expression in Pparβ/δ+/+ mice, but not in Pparβ/δ-/- mice...
October 20, 2016: Journal of Biological Chemistry
Thiago Almeida Pereira, Wing-Kin Syn, Frederico Figueiredo Amâncio, Pedro Henrique Diniz Cunha, Julia Fonseca Morais Caporali, Guilherme Vaz de Melo Trindade, Elisângela Trindade Santos, Márcia Maria Souza, Zilton Araújo Andrade, Rafal P Witek, William Evan Secor, Fausto Edmundo Lima Pereira, José Roberto Lambertucci, Anna Mae Diehl
BACKGROUND: Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection...
October 2016: PLoS Neglected Tropical Diseases
X M Chen, F Q Li, S Yan, X C Wu, C L Tang
OBJECTIVE: To investigate the anti-inflammation effects by activation of the cholinergic anti-inflammatory pathway and its mechanisms in non-alcoholic steatohepatitis (NASH) model mice. METHODS: 6-week-old male C57BL/6J (B6) mice were randomly divided into four groups: the first group was normal mice, injected with saline; the second group was normal mice, injected with nicotine; the third group was NASH model mice, injected with saline; the fourth group was NASH model mice, injected with nicotine...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Toshihiko Kawasaki, Kan-Yun Hata, Daisuke Kinoshita, Masaki Takayama, Hideyuki Okuda, Shigeto Mizuno, Masatoshi Kudo
PURPOSE: Contrast-enhanced sonography increases negative enhancement in the Kupffer phase after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We compared contrast-enhanced sonography with B-mode sonography for guidance of radiofrequency ablation (RFA) of HCC after TACE. METHODS: After TACE was performed, 18 nodules in 12 patients were treated by B-mode sonography guided RFA, while 22 nodules in 18 patients were treated by contrast-enhanced sonography-guided RFA...
2016: Digestive Diseases
Nursel Gül, Nuri Yiğit, Fulya Saygılı, Ebru Demirel, Ceren Geniş
We used transmission electron microscopy to examine the cytotoxic effects of the second-generation anticoagulant rodenticides difenacoum and brodifacoum on rat liver. A single dose of difenacoum or brodifacoum was administered to rats by gastric gavage and liver samples were taken after 24 h, four days or seven days. In the livers of rats treated with difenacoum for 24 h, hepatocytes typically showed increased numbers of lysosomes, as well as enlargement of both the perinuclear space and the cisternae of the rough endoplasmic reticulum (RER), while sinusoids were irregularly shaped and contained Kupffer cells...
September 1, 2016: Arhiv za Higijenu Rada i Toksikologiju
Yanqing Zhang, Cheng Wang, Yunli Tian, Fengxiao Zhang, Wenjing Xu, Xiangrao Li, Zhiping Shu, Yan Wang, Kai Huang, Dan Huang
Activation of Kupffer cells (KCs) by gut-derived endotoxin plays a pivotal role in the pathogenesis of alcoholic liver diseases (ALD). Limiting the activation of resident KCs attenuates chronic ethanol-induced liver steatosis and injury. Poly (ADP-ribose) polymerase (PARP)-1 is suggested to play a role in a number of chronic inflammatory diseases. In this study, we found a significant increase of hepatic PARP activity in mice with short-term and long-term ethanol-induced ALD. Male mice on a long-term ethanol diet exhibited severe hepatic steatosis and apoptosis and enhanced KC activation and neutrophil infiltration...
October 13, 2016: American Journal of Pathology
Guo Yuan, You Yu, Li Ji, Xu Jie, Li Yue, Yang Kang, Gong Jianping, Liu Zuojin
BACKGROUND: Lipopolysaccharide (LPS) preconditioning is known to attenuate hepatic ischemia/reperfusion injury (I/RI); however, the precise mechanism remains unclear. This study investigated the role of receptor-interacting protein 140 (RIP140) on the protective effect of LPS preconditioning in hepatic I/RI involving Kupffer cells (KCs). METHODS: Sprague-Dawley rats underwent 70% hepatic ischemia for 90 minutes. LPS (100 μg/kg) was injected intraperitoneally 24 hours before ischemia...
2016: PloS One
Katalin Jemnitz, Attila Bátai-Konczos, Mónika Szabó, Enikő Ioja, Orsolya Kolacsek, Tamás I Orbán, György Török, László Homolya, Eszter Kovács, István Jablonkai, Zsuzsa Veres
Increasing number of papers demonstrate that Kupffer cells (KCs) play a role in the development of drug induced liver injury (DILI). Furthermore, elevated intracellular Ca(2+) level of hepatocytes is considered as a common marker of DILI. Here we applied an in vitro model based on hepatocyte mono- and hepatocyte/KC co-cultures (H/KC) isolated from transgenic rats stably expressing the GCaMP2 fluorescent Ca(2+) sensor protein to investigate the effects of polycationic (G5), polyanionic (G4.5) and polyethylene-glycol coated neutral (G5 Peg) dendrimers known to accumulate in the liver, primarily in KCs...
October 4, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Masato Nakasone, Kazuhiro Nakaso, Yosuke Horikoshi, Takehiko Hanaki, Yoshinori Kitagawa, Toru Takahashi, Yoshimi Inagaki, Tatsuya Matsura
BACKGROUND: Sepsis is a syndrome triggered by endotoxin lipopolysaccharide (LPS) during bacterial infection. Sepsis sometimes recurs, with the second sepsis giving rise to a different phenotype because of disease modification by the preceding sepsis. Such a protective modification is called a preconditioning (PC) effect. PC is an endogenous protective mechanism by which sublethal damage confers tolerance to a subsequent lethal load. Oxidative stress is one of the important pathogenetic mechanisms that occur in sepsis...
September 2016: Yonago Acta Medica
Hiroyuki Nakashima, Masahiro Nakashima, Manabu Kinoshita, Masami Ikarashi, Hiromi Miyazaki, Hiromi Hanaka, Junko Imaki, Shuhji Seki
We have recently reported that Kupffer cells consist of two subsets, radio-resistant resident CD68+ Kupffer cells and radio-sensitive recruited CD11b+ Kupffer cells/macrophages (Mφs). Non-alcoholic steatohepatitis (NASH) is characterized not only by hepatic steatosis but also chronic inflammation and fibrosis. In the present study, we investigated the immunological mechanism of diet-induced steatohepatitis in fibroblast growth factor 5 (FGF5) deficient mice. After consumption of a high fat diet (HFD) for 8 weeks, FGF5 null mice developed severe steatohepatitis and fibrosis resembling human NASH...
October 6, 2016: Scientific Reports
Maiko Terada, Kenichi Horisawa, Shizuka Miura, Yasuo Takashima, Yasuyuki Ohkawa, Sayaka Sekiya, Kanae Matsuda-Ito, Atsushi Suzuki
Intrahepatic cholangiocarcinoma (ICC) is a malignant epithelial neoplasm composed of cells resembling cholangiocytes that line the intrahepatic bile ducts in portal areas of the hepatic lobule. Although ICC has been defined as a tumor arising from cholangiocyte transformation, recent evidence from genetic lineage-tracing experiments has indicated that hepatocytes can be a cellular origin of ICC by directly changing their fate to that of biliary lineage cells. Notch signaling has been identified as an essential factor for hepatocyte conversion into biliary lineage cells at the onset of ICC...
October 4, 2016: Scientific Reports
Capucine L Grandjean, Fabricio Montalvao, Susanna Celli, David Michonneau, Beatrice Breart, Zacarias Garcia, Mario Perro, Olivier Freytag, Christian A Gerdes, Philippe Bousso
Anti-CD20 monoclonal antibodies (mAbs) represent an effective treatment for a number of B cell malignancies and autoimmune disorders. Glycoengineering of anti-CD20mAb may contribute to increased anti-tumor efficacy through enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP) as reported by in vitro studies. However, where and how glycoengineered Ab may potentiate therapeutic responses in vivo is yet to be elucidated. Here, we have performed mouse liver transplants to demonstrate that the liver is sufficient to mediate systemic B cells depletion after anti-CD20 treatment...
October 4, 2016: Scientific Reports
Christopher Leung, Chandana B Herath, Zhiyuan Jia, Sof Andrikopoulos, Bronwyn E Brown, Michael J Davies, Leni R Rivera, John B Furness, Josephine M Forbes, Peter W Angus
AIM: To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS: Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs...
September 21, 2016: World Journal of Gastroenterology: WJG
Chun-Mu Miao, Xiao-Wei Jiang, Kun He, Pei-Zhi Li, Zuo-Jin Liu, Ding Cao, Zhi-Bing Ou, Jian-Ping Gong, Chang-An Liu, Yao Cheng
The nucleotide-binding and oligomerization domain-like receptor 3 (NLRP3) inflammasome participates in the pathogenesis of acute liver injury during sepsis. Bone marrow mesenchymal stem cells (BMSCs) attenuate sepsis through prostaglandin E 2 (PGE2) by increasing the interleukin-10 (IL-10) production of macrophages; moreover, NLRP3 inflammasome assembly is effectively regulated by IL-10 during infection. Whether BMSCs have an effect on the activation of the NLRP3 inflammasome and its underlying mechanism is unclear...
September 22, 2016: Immunology Letters
Shiori Takashima, Kenichi Ikejima, Kumiko Arai, Junko Yokokawa, Kazuyoshi Kon, Shunhei Yamashina, Sumio Watanabe
Strategies for prevention and treatment of nonalcoholic steatohepatitis (NASH) remain to be established. Here, we evaluated the effect of glycine on metabolic steatohepatitis in genetically obese, diabetic KK-A(y) mice. Male KK-A(y) mice were fed a diet containing 5% glycine for 4 weeks, and liver pathology was evaluated. Hepatic mRNA levels for lipid-regulating molecules, cytokines/chemokines, and macrophage M1/M2 markers were determined by real time RT-PCR. Hepatic expression of natural killer (NK) T cells was analyzed by flow cytometry...
September 22, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Ravinder Reddy Gaddam, Robin Fraser, Alireza Badiei, Stephen Chambers, Victoria C Cogger, David G Le Couteur, Madhav Bhatia
Sepsis remains a common clinical problem with significant mortality. Activation of the Kupffer cells during sepsis is associated with systemic inflammatory response and multiple organ failure. Kupffer cell activation also leads to structural changes in the liver sinusoidal endothelial cells (LSECs) during endotoxemia. However, these effects remain to be elucidated in caecal-ligation and puncture (CLP)-induced polymicrobial sepsis. To investigate the role of Kupffer cells on LSECs fenestrae and inflammation during CLP-induced sepsis, sepsis was induced by CLP and mice were treated with gadolinium chloride (GdCl3) before CLP-induced sepsis, to inactivate Kupffer cells...
September 19, 2016: Shock
Judit Pomothy, Gergely Szombath, Patrik Rokonál, Gábor Mátis, Zsuzsanna Neogrády, Torsten Steinmetzer, Erzsébet Pászti-Gere
Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1) were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA...
2016: BioMed Research International
Len Verbeke, Inge Mannaerts, Robert Schierwagen, Olivier Govaere, Sabine Klein, Ingrid Vander Elst, Petra Windmolders, Ricard Farre, Mathias Wenes, Massimiliano Mazzone, Frederik Nevens, Leo A van Grunsven, Jonel Trebicka, Wim Laleman
Hepatic inflammation drives hepatic stellate cells (HSC), resulting in liver fibrosis. The Farnesoid-X receptor (FXR) antagonizes inflammation through NF-κB inhibition. We investigated preventive and therapeutic effects of FXR agonist obeticholic acid (OCA) on hepatic inflammation and fibrosis in toxic cirrhotic rats. Cirrhosis was induced by thioacetamide (TAA) intoxication. OCA was given during or after intoxication with vehicle-treated rats as controls. At sacrifice, fibrosis, hemodynamic and biochemical parameters were assessed...
2016: Scientific Reports
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