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https://www.readbyqxmd.com/read/27906627/oxidized-low-density-lipoproteins-enhance-expression-and-activity-of-cd39-and-cd73-in-the-human-aortic-valve-endothelium
#1
Ewa Kaniewska-Bednarczuk, Michał Mielcarek, Adrian H Chester, Ewa M Slominska, Magdi H Yacoub, Ryszard T Smolenski
Extracellular nucleotides regulate thrombosis, inflammation, and immune response. Ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and ecto-5'-nucleotidase (CD73) convert extracellular nucleotides in a sequential order: ATP to ADP, AMP, and then to adenosine. In this study, we aimed to test an effect of oxidized low-density lipoprotein (ox-LDL) on CD39 and CD73 in endothelial cells. Human aortic valve endothelial cells were exposed to ox-LDL for 24-48 h. Next, the activity, protein expression, and mRNA transcripts level of CD39 and CD73 were characterized by an incubation with ATP or AMP followed by high-performance liquid chromatography analysis of media as well as western blots and qPCR...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27899277/protective-role-of-hypoxia-inducible-factor-1%C3%AE-dependent-cd39-and-cd73-in-fulminant-acute-liver-failure
#2
Eunyoung Tak, Dong-Hwan Jung, Seok-Hwan Kim, Gil-Chun Park, Dae Young Jun, Jooyoung Lee, Bo-Hyun Jung, Varvara A Kirchner, Shin Hwang, Gi-Won Song, Sung-Gyu Lee
Acute liver failure (ALF) is a severe life-threatening disease which usually arises in patients with-irreversible liver illnesses. Although human ectonucleotide triphosphate diphosphohydrolase-1, E-NTPDase1 (CD39) and ecto-5'-nucleotidase, Ecto5'NTase (CD73) are known to protect tissues from ALF, the expression and function of CD39 and CD73 during ALF are currently not fully investigated. We tested whether CD39 and CD73 are upregulated by hypoxia inducible factor (HIF)-1α, and improve ischemic tolerance to ALF...
November 27, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27895775/high-expression-of-cd39-in-gastric-cancer-reduces-patient-outcome-following-radical-resection
#3
Xiao-Yan Cai, Xue-Fei Wang, Jun Li, Jiang-Nan Dong, Jiang-Qi Liu, Neng-Ping Li, Bei Yun, Rong-Long Xia, Jing Qin, Yi-Hong Sun
Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), also known as cluster of differentiation (CD)39, is the rate-limiting enzyme in the generation of immunosuppressive adenosine and is important in tumor progression. The present study evaluated the expression of CD39(+) and CD39(+) forkhead box P3 (FoxP3)(+) regulatory T (Treg) cells in gastric cancer (GC), and determined their prognostic roles in patients with GC following radical resection. It was observed that CD39 was expressed at significantly higher rates in tumor tissues as compared with paired peritumoral tissues...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27862653/response-to-letter-to-the-editor-adenosine-producing-mesenchymal-stromal-cells
#4
Erja Kerkelä
Adenosine signaling has been described as one of the many immunosuppressive mechanisms of mesenchymal stromal cells (MSCs). Central players in adenosine signaling are the ectonucleotidases CD39 and CD73, which convert ADP/ATP to AMP and AMP to adenosine, respectively. CD73 is one of the three phenotypic markers of MSCs and thus, highly expressed on MSCs. Instead, there has been conflicting results whether MSCs intrinsically express CD39 or not. Stem Cells 2016.
November 11, 2016: Stem Cells
https://www.readbyqxmd.com/read/27856402/the-expression-of-ntpdase1-and-2-of-leishmania-infantum-chagasi-in-bacterial-and-mammalian-cells-comparative-expression-refolding-and-nucleotidase-characterization
#5
M S Bastos, A Tremblay, J M Agripino, I L A Rabelo, L P Barreto, J Pelletier, J Lecka, A Silva-Júnior, G C Bressan, M R Almeida, J Sévigny, J L R Fietto
Visceral Leishmaniasis (VL) represents an important global health problem in several warm countries around the world. The main targets in this study are the two nucleoside triphosphate diphosphohydrolases (NTPDases) from Leishmania infantum chagasi that are the main etiologic agent of VL in the New World. These enzymes, called LicNTPDase1 and -2, are homologous to members 5 and 6 of the mammalian E-NTPDase/CD39 superfamily of enzymes. These enzymes hydrolyze nucleotides and accordingly can participate in the purine salvage pathways and in the modulation of purinergic signaling through the extracellular nucleotide-dependent host immune responses...
November 14, 2016: Protein Expression and Purification
https://www.readbyqxmd.com/read/27830476/production-of-heterozygous-alpha-1-3-galactosyltransferase-ggta1-knock-out-transgenic-miniature-pigs-expressing-human-cd39
#6
Kimyung Choi, Joohyun Shim, Nayoung Ko, Heejong Eom, Jiho Kim, Jeong-Woong Lee, Dong-Il Jin, Hyunil Kim
Production of transgenic pigs for use as xenotransplant donors is a solution to the severe shortage of human organs for transplantation. The first barrier to successful xenotransplantation is hyperacute rejection, a rapid, massive humoral immune response directed against the pig carbohydrate GGTA1 epitope. Platelet activation, adherence, and clumping, all major features of thrombotic microangiopathy, are inevitable results of immune-mediated transplant rejection. Human CD39 rapidly hydrolyzes ATP and ADP to AMP; AMP is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine, an anti-thrombotic and cardiovascular protective mediator...
November 9, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27807997/adenosine-receptors-expression-in-cardiac-fibroblasts-of-patients-with-left-ventricular-dysfunction-due-to-valvular-disease
#7
Silvia Del Ry, Manuela Cabiati, Veronica Della Latta, Stefania Zimbone, Mariarita Natale, Pietro Enea Lazzerini, Francesco Diciolla, Pier Leopoldo Capecchi, Franco Laghi-Pasini, Maria Aurora Morales
CONTEXT: Adenosine restores tissue homeostasis through the interaction with its membrane receptors (AR) expressed on fibroblasts, endothelial cells, smooth muscle cells and leukocytes, but their modulation is still not fully understood. OBJECTIVE: To evaluate whether changes in the transcriptomic profiling of adenosine receptors (AR) occur in cardiac fibroblasts (CF) of patients (pts) with LV dysfunction due to valvular disease (V). The secondary aim was to compare in the same pts the results obtained at cardiac level with those found in circulating leukocytes...
November 3, 2016: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/27793266/purinergic-signaling-and-infection-by-leishmania-a-new-approach-to-evasion-of-the-immune-response
#8
REVIEW
Amanda Braga de Figueiredo, Miriam Conceicao Souza-Testasicca, Luis Carlos Crocco Afonso
Infection by protozoan parasites is part of the most common Tropical Neglected Diseases. In the case of leishmaniasis, several millions of people are at risk of contracting the disease. In spite of innumerous studies that elucidated the immune response capable of killing the parasite, the understanding of the evasion mechanisms utilized by the parasite to survive within the very cell responsible for its destruction is still incomplete. In this review, we offer a new approach to the control of the immune response against the parasite...
August 2016: Biomedical Journal
https://www.readbyqxmd.com/read/27783946/ahr-activation-is-protective-against-colitis-driven-by-t-cells-in-humanized-mice
#9
Jeremy A Goettel, Roopali Gandhi, Jessica E Kenison, Ada Yeste, Gopal Murugaiyan, Sharmila Sambanthamoorthy, Alexandra E Griffith, Bonny Patel, Dror S Shouval, Howard L Weiner, Scott B Snapper, Francisco J Quintana
Existing therapies for inflammatory bowel disease that are based on broad suppression of inflammation result in variable clinical benefit and unwanted side effects. A potential therapeutic approach for promoting immune tolerance is the in vivo induction of regulatory T cells (Tregs). Here we report that activation of the aryl hydrocarbon receptor using the non-toxic agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces human Tregs in vitro that suppress effector T cells through a mechanism mediated by CD39 and Granzyme B...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27782859/mesenchymal-stromal-cells-derived-from-cervical-cancer-produce-high-amounts-of-adenosine-to-suppress-cytotoxic-t-lymphocyte-functions
#10
María de Lourdes Mora-García, Rosario García-Rocha, Omar Morales-Ramírez, Juan José Montesinos, Benny Weiss-Steider, Jorge Hernández-Montes, Luis Roberto Ávila-Ibarra, Christian Azucena Don-López, Marco Antonio Velasco-Velázquez, Vianey Gutiérrez-Serrano, Alberto Monroy-García
BACKGROUND: In recent years, immunomodulatory mechanisms of mesenchymal stem/stromal cells (MSCs) from bone marrow and other "classic" sources have been described. However, the phenotypic and functional properties of tumor MSCs are poorly understood. The aim of this study was to analyze the immunosuppressive capacity of cervical cancer-derived MSCs (CeCa-MSCs) on effector T lymphocytes through the purinergic pathway. METHODS: We determined the expression and functional activity of the membrane-associated ectonucleotidases CD39 and CD73 on CeCa-MSCs and normal cervical tissue-derived MSCs (NCx-MSCs)...
October 26, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27781068/chondrogenic-potency-analyses-of-donor-matched-chondrocytes-and-mesenchymal-stem-cells-derived-from-bone-marrow-infrapatellar-fat-pad-and-subcutaneous-fat
#11
John Garcia, Claire Mennan, Helen S McCarthy, Sally Roberts, James B Richardson, Karina T Wright
Autologous chondrocyte implantation (ACI) is a cell-based therapy that has been used clinically for over 20 years to treat cartilage injuries more efficiently in order to negate or delay the need for joint replacement surgery. In this time, very little has changed in the ACI procedure, but now many centres are considering or using alternative cell sources for cartilage repair, in particular mesenchymal stem cells (MSCs). In this study, we have tested the chondrogenic potential of donor-matched MSCs derived from bone marrow (BM), infrapatellar fat pad (FP), and subcutaneous fat (SCF), compared to chondrocytes...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27766282/induction-of-gut-regulatory-cd39-t-cells-by-teriflunomide-protects-against-eae
#12
Javier Ochoa-Repáraz, Sara L Colpitts, Christopher Kircher, Eli J Kasper, Kiel M Telesford, Sakhina Begum-Haque, Anudeep Pant, Lloyd H Kasper
OBJECTIVE: To determine whether as an orally delivered treatment, teriflunomide, an inhibitor of the mitochondrial enzyme dihydroorotate dehydrogenase approved to treat relapsing forms of multiple sclerosis, could affect gut-associated lymphoid tissue (GALT) immune responses functionally. METHODS: C57BL/6 mice were treated orally with teriflunomide and flow cytometric analysis of immune GALT cells performed ex vivo, and adoptive transfer experiments were used to test the protective effects of GALT regulatory T (Treg) cells...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/27756600/impact-of-cardiac-specific-expression-of-cd39-on-myocardial-infarct-size-in-mice
#13
Stephen B Smith, Zhaobin Xu, Tatiana Novitskaya, Bo Zhang, Elena Chepurko, Xin-An Pu, Debra G Wheeler, Mark Ziolo, Richard J Gumina
AIMS: Prior work suggests that ischemic preconditioning increases the level of CD39 in the heart and contributes to cardiac protection. Therefore, we examined if targeted cardiac expression of CD39 protects against myocardial injury. MAIN METHODS: Mice with cardiac-specific expression of human CD39 (αMHC/hCD39-Tg) were generated, characterized and subjected to left coronary artery ischemia-reperfusion injury and infarct size at 24h following injury quantified. KEY FINDINGS: αMHC/hCD39-Tg mice have increased in cardiac ATPase and ADPase activity compared to WT littermates...
October 15, 2016: Life Sciences
https://www.readbyqxmd.com/read/27749555/overexpression-of-cd39-in-hepatocellular-carcinoma-is-an-independent-indicator-of-poor-outcome-after-radical-resection
#14
Xiao-Yan Cai, Xiao-Chun Ni, Yong Yi, Hong-Wei He, Jia-Xing Wang, Yi-Peng Fu, Jian Sun, Jian Zhou, Yun-Feng Cheng, Jian-Jun Jin, Jia Fan, Shuang-Jian Qiu
Nucleoside triphosphate diphosphohydrolase-1 (ENTPD1/CD39) is the rate-limiting enzyme in a cascade leading to the generation of immunosuppressive adenosine and plays an important role in tumor progression. This study aimed to evaluate the expression of CD39 and CD39Foxp3 regulatory T cells (Tregs) and to determine their prognostic role in patients with hepatocellular carcinoma (HCC) after radical resection.Immunohistochemistry (IHC) and double IHC were used to analyze CD39 expression or the expression of CD39 and Foxp3 in a cohort of 324 HCC patients who underwent curative resection...
October 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27730511/p2x7-receptor-signaling-contributes-to-sepsis-associated-brain-dysfunction
#15
Luiz Eduardo Baggio Savio, Mariana G Juste Andrade, Paola de Andrade Mello, Patrícia Teixeira Santana, Aline Cristina Abreu Moreira-Souza, Janaína Kolling, Aline Longoni, Linda Feldbrügge, Yan Wu, Angela T S Wyse, Simon C Robson, Robson Coutinho-Silva
Sepsis results in unfettered inflammation, tissue damage, and multiple organ failure. Diffuse brain dysfunction and neurological manifestations secondary to sepsis are termed sepsis-associated encephalopathy (SAE). Extracellular nucleotides, proinflammatory cytokines, and oxidative stress reactions are associated with delirium and brain injury, and might be linked to the pathophysiology of SAE. P2X7 receptor activation by extracellular ATP leads to maturation and release of IL-1β by immune cells, which stimulates the production of oxygen reactive species...
October 11, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27720959/tgf-%C3%AE-1-and-contact-mediated-suppression-by-cd4-cd25-cd127-t-regulatory-cells-of-patients-with-self-limiting-hepatitis-e
#16
Sanjay B Rathod, Anuradha S Tripathy
BACKGROUND AND AIM: Literature on the role of Regulatory T cells (Tregs) in acute viral infections is limited. Having established that the Tregs in self-limiting hepatitis E infection are elevated and functional, this study has focused on characterizing the specificity, phenotypes and identifying the molecules or factors responsible for enhancement of Treg cells and abrogation of Treg-mediated suppression in hepatitis E. METHODS: HEV rORF2p specific (a) Treg frequency, subset analysis and expression of surface and intracellular markers on Tregs and CFSE based functional analysis by flow cytometry (b) key cytokines quantification by multiplex (c) suppressive functional assay in the presence of anti-TGF-β1 or anti-IL-10 or both antibodies or Transwell insert or in combination were performed on samples from 58 acute patients (AVH-E), 45 recovered individuals from hepatitis E and 55 controls...
October 6, 2016: Human Immunology
https://www.readbyqxmd.com/read/27697858/il-2-variant-circumvents-icos-regulatory-t-cell-expansion-and-promotes-nk-cell-activation
#17
Geok Choo Sim, Chengwen Liu, Ena Wang, Hui Liu, Caitlin Creasy, Zhimin Dai, Willem W Overwijk, Jason Roszik, Francesco M Marincola, Patrick Hwu, Elizabeth A Grimm, Laszlo G Radvanyi
Clinical responses to high-dose IL-2 therapy are limited due to selective expansion of CD4+CD25+oxp3+ T-regulatory cells (Tregs) especially ICOS+Tregs, rather than NK cells and effector T cells. These ICOS+Tregs are highly suppressive and constitutively express high levels of IL-2Ralpha (CD25) and CD39. Here, we characterized the effect of a mutant form of IL-2 (F42K), which preferentially binds to the lower affinity IL-2Rbetagamma with reduced binding to CD25, on Tregs, effector NK cells, and T-cell subsets...
October 3, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27677162/immune-tolerance-properties-of-the-testicular-tissue-as-a-viral-sanctuary-site-in-art-treated-hiv-infected-adults
#18
Mohammad-Ali Jenabian, Cecilia T Costiniuk, Vikram Mehraj, Feras M Ghazawi, Rémi Fromentin, Joëlle Brousseau, Pierre Brassard, Maud Bélanger, Petronela Ancuta, Reina Bendayan, Nicolas Chomont, Jean-Pierre Routy
OBJECTIVE: HIV persistence in long-lived infected cells and in anatomical sanctuary sites are major hurdles to HIV eradication. Testicular tissue may represent a significant viral sanctuary site as it constitutes an immunologically-privileged compartment. We assessed immuno-tolerance properties of the testicular tissue in individuals receiving suppressive ART. DESIGN AND METHODS: Testicular tissue and matched blood samples were collected from 6 virally suppressed adults and 10 HIV-uninfected controls prior to gender reassignment surgery...
September 24, 2016: AIDS
https://www.readbyqxmd.com/read/27665459/the-role-of-adenosinergic-pathway-in-human-autoimmune-diseases
#19
Ke Dong, Zhao-Wei Gao, Hui-Zhong Zhang
Autoimmune diseases are characterized by the abnormal immune response against self-tissue, which are caused by the failure of nature immune homeostasis. Nature immune homeostasis represents the normal state of appropriate immune response to nonself-antigen and unresponsiveness to self-antigens. In normal situation, immune homeostasis is regulated by immunosuppressive signal and immunostimulating signal together. Accumulating data have demonstrated that the adenosinergic pathway played key roles in immune suppression and shield body from an excessive inflammatory response...
September 24, 2016: Immunologic Research
https://www.readbyqxmd.com/read/27663683/human-adenosine-deaminases-ada1-and-ada2-bind-to-different-subsets-of-immune-cells
#20
Yuliia Kaljas, Chengqian Liu, Maksym Skaldin, Chengxiang Wu, Qing Zhou, Yuanan Lu, Ivona Aksentijevich, Andrey V Zavialov
At sites of inflammation and tumor growth, the local concentration of extracellular adenosine rapidly increases and plays a role in controlling the immune responses of nearby cells. Adenosine deaminases ADA1 and ADA2 (ADAs) decrease the level of adenosine by converting it to inosine, which serves as a negative feedback mechanism. Mutations in the genes encoding ADAs lead to impaired immune function, which suggests a crucial role for ADAs in immune system regulation. It is not clear why humans and other mammals possess two enzymes with adenosine deaminase activity...
September 23, 2016: Cellular and Molecular Life Sciences: CMLS
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