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https://www.readbyqxmd.com/read/29780382/extracellular-purine-metabolism-is-the-switchboard-of-immunosuppressive-macrophages-and-a-novel-target-to-treat-diseases-with-macrophage-imbalances
#1
Anna Ohradanova-Repic, Christian Machacek, Celine Charvet, Franck Lager, Delphine Le Roux, René Platzer, Vladimir Leksa, Goran Mitulovic, Thomas R Burkard, Gerhard J Zlabinger, Michael B Fischer, Vincent Feuillet, Gilles Renault, Stephan Blüml, Miroslav Benko, Miloslav Suchanek, Johannes B Huppa, Takami Matsuyama, Artur Cavaco-Paulo, Georges Bismuth, Hannes Stockinger
If misregulated, macrophage (Mϕ)-T cell interactions can drive chronic inflammation thereby causing diseases, such as rheumatoid arthritis (RA). We report that in a proinflammatory environment, granulocyte-Mϕ (GM-CSF)- and Mϕ colony-stimulating factor (M-CSF)-dependent Mϕs have dichotomous effects on T cell activity. While GM-CSF-dependent Mϕs show a highly stimulatory activity typical for M1 Mϕs, M-CSF-dependent Mϕs, marked by folate receptor β (FRβ), adopt an immunosuppressive M2 phenotype. We find the latter to be caused by the purinergic pathway that directs release of extracellular ATP and its conversion to immunosuppressive adenosine by co-expressed CD39 and CD73...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29775846/reproductive-stage-and-sex-steroid-hormone-levels-influence-the-expression-of-mesenchymal-stromal-cell-msc-markers-in-the-equine-endometrium
#2
B Elisabeth Rink, Juliane Kuhl, Cristina L Esteves, Hilari M French, Elaine Watson, Christine Aurich, F Xavier Donadeu
Mesenchymal stem or stromal cells (MSCs) play key roles in tissue homeostasis. In the cyclic equine endometrium, this may be regulated by changes in serum concentrations of sex steroid hormones. This study was designed to investigate the changes in endometrial expression of MSC markers during reproductive cycles in mares and the influence of sex steroid hormones on endometrial MSC proliferation in vitro. Endometrial biopsies were collected from pony mares at different reproductive stages (estrus; day 5 and 13 after ovulation; seasonal anestrus; 20 h and 7days post-partum; n = 5 per stage) and were analyzed by RT-qPCR...
May 4, 2018: Theriogenology
https://www.readbyqxmd.com/read/29769837/the-role-of-extracellular-adenosine-generation-in-the-development-of-autoimmune-diseases
#3
REVIEW
F Morandi, A L Horenstein, R Rizzo, F Malavasi
Adenosine (ADO) is an immunosuppressive molecule, which suppresses the immune responses by interacting with specific receptors expressed by immune effector cells. ADO is produced from ATP through the enzymatic activities of CD39 and CD73. Alternatively, ADO can be generated starting from NAD+ , which is metabolized by the concerted action of CD38, CD203a/PC-1, and CD73. The role of ADO in immunity has been characterized in the last years in physiology and in pathological settings. This review examines a panel of reports focused on the functions of ADO in the context of human autoimmune/inflammatory diseases and the selected animal models...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29768259/precise-intradermal-injection-of-nanofat-derived-stromal-cells-combined-with-platelet-rich-fibrin-improves-the-efficacy-of-facial-skin-rejuvenation
#4
Zhi-Jie Liang, Xiang Lu, De-Quan Li, Yi-Dan Liang, Dan-Dan Zhu, Fang-Xiao Wu, Xiao-Lin Yi, Ning He, Yan-Qing Huang, Chao Tang, Hong-Mian Li
BACKGROUND/AIMS: The rejuvenation properties of nanofat grafting have been described in recent years. However, it is not clear whether the clinical efficacy of the procedure is attributable to stem cells or linked to other components of adipose tissue. In this study we isolated nanofat-derived stem cells (NFSCs) to observe their biological characteristics and evaluate the efficacy of precise intradermal injection of nanofat combined with platelet-rich fibrin (PRF) in patients undergoing facial rejuvenation treatment...
May 11, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29765418/isolation-and-characterisation-of-mesenchymal-stem-cells-from-rat-bone-marrow-and-the-endosteal-niche-a-comparative-study
#5
Norhayati Yusop, Paul Battersby, Amr Alraies, Alastair J Sloan, Ryan Moseley, Rachel J Waddington
Within bone, mesenchymal stromal cells (MSCs) exist within the bone marrow stroma (BM-MSC) and the endosteal niche, as cells lining compact bone (CB-MSCs). This study isolated and characterised heterogeneous MSC populations from each niche and subsequently investigated the effects of extensive cell expansion, analysing population doublings (PDs)/cellular senescence, colony-forming efficiencies (CFEs), MSC cell marker expression, and osteogenic/adipogenic differentiation. CB-MSCs and BM-MSCs demonstrated similar morphologies and PDs, reaching 100 PDs...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29761109/mesenchymal-stem-cells-differentiate-to-endothelial-cells-using-recombinant-vascular-endothelial-growth-factor-a
#6
Mohsen Khaki, Ali Hatef Salmanian, Hamid Abtahi, Ali Ganji, Ghasem Mosayebi
Background: Vascular endothelial growth factor-A (VEGF-A), an endothelial cell-specific mitogen produced by various cell types, plays important roles in cell differentiation and proliferation. In this study we investigated the effect of recombinant VEGF-A on differentiation of mesenchymal stem cells (MSCs) to endothelial cells (ECs). Methods: VEGF-A was expressed in E. coli BL21 (DE3) and BL21 pLysS competent cells with the pET32a expression vector. Recombinant VEGF-A protein expression was verified by SDS-PAGE and western blotting...
April 2018: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29759563/targeting-the-tumor-promoting-effects-of-adenosine-in-chronic-lymphocytic-leukemia
#7
REVIEW
Yiqing Cai, Lili Feng, Xin Wang
Chronic lymphocytic leukemia (CLL) is a hematological malignancy which is characterized by progressive accumulation of functionally deficient B cells in blood, bone marrow, and lymphatic tissue. The tumor microenvironment (TME) appears to play a critical role in genesis and progression of CLL. High levels of extracellular adenosine (ADO) are detected in CLL as a consequence of expression of ecto-enzymes, such as CD39 and CD73. Extracellular ADO exhibits a broad range of effects on cell cycle control, immunoregulation, angiogenesis and cytokine regulation through both direct and indirect mechanisms...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29758241/targeting-the-cd73-adenosine-axis-in-immuno-oncology
#8
REVIEW
David Allard, Pavel Chrobak, Bertrand Allard, Nouredin Messaoudi, John Stagg
The ectonucleotidases CD39 and CD73 are cell surface enzymes that catabolize the breakdown of extracellular ATP into adenosine. As such, they constitute critical components of the extracellular purinergic pathway and play important roles in maintaining tissue and immune homeostasis. With the coming of age of cancer immunotherapy, ectonucleotidases and adenosine receptors have emerged as novel therapeutic targets to enhance antitumor immune responses. With early-phase clinical trials showing promising results, it is becoming increasingly important to decipher the distinct mechanisms-of-action of adenosine-targeting agents, identify patients that will benefit from these agents and rationally develop novel synergistic combinations...
May 11, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29751114/very-low-numbers-of-cd4-foxp3-tregs-expanded-in-donors-via-tl1a-ig-and-low-dose-il-2-exhibit-a-distinct-activation-functional-profile-and-suppress-gvhd-in-a-pre-clinical-model
#9
Sabrina Copsel, Dietlinde Wolf, Brandon Kale, Henry Barreras, Casey O Lightbourn, Cameron S Bader, W Alperstein, Norman H Altman, Krishna V Komanduri, Robert B Levy
Regulatory T cells (Tregs) are essential for the maintenance of tolerance and immune homeostasis. In allogeneic hematopoietic stem cell transplantation (aHSCT), transfer of appropriate Treg numbers is a promising therapy for the prevention of graft-versus-host disease (GVHD). We have recently reported a novel approach which induces the marked expansion and selective activation of Tregs in vivo by targeting TNF receptor superfamily 25 (TNFRSF25) and CD25. A potential advance to promote clinical application of Treg cells to ameliorate GVHD and other disorders would be the generation of more potent Treg populations...
May 8, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29745882/the-adenosinergic-system-a-potential-player-in-the-pathogenesis-of-anca-associated-vasculitis
#10
REVIEW
Lovis Kling, Bernhard K Krämer, Benito A Yard, Anna-Isabelle Kälsch
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially lethal autoimmune disease whose pathology comprises disturbed T cell differentiation and functionality accompanied by dysfunctional autoreactive immunoglobulin development, culminating in destructive innate immune response as well. Purines, adenine nucleotides and adenosine in particular, have been elucidated as potent extracellular mediators for fine adjustment of these pivotal processes establishing human immunity. Therefore, the extracellular purinergic microenvironment is under control of ectonucleotidases CD39 and CD73 degrading pro-inflammatory adenosine triphosphate (ATP) to anti-inflammatory adenosine as well as adenosine deaminase bound to CD26 deactivating adenosine...
May 3, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29742141/cd39-is-upregulated-during-activation-of-mouse-and-human-t-cells-and-attenuates-the-immune-response-to-listeria-monocytogenes
#11
Friederike Raczkowski, Anne Rissiek, Isabell Ricklefs, Kirsten Heiss, Valéa Schumacher, Kira Wundenberg, Friedrich Haag, Friedrich Koch-Nolte, Eva Tolosa, Hans-Willi Mittrücker
The ectoenzymes CD39 and CD73 degrade extracellular ATP to adenosine. ATP is released by stressed or damaged cells and provides pro-inflammatory signals to immune cells through P2 receptors. Adenosine, on the other hand, suppresses immune cells by stimulating P1 receptors. Thus, CD39 and CD73 can shape the quality of immune responses. Here we demonstrate that upregulation of CD39 is a consistent feature of activated conventional CD4+ and CD8+ T cells. Following stimulation in vitro, CD4+ and CD8+ T cells from human blood gained surface expression of CD39 but displayed only low levels of CD73...
2018: PloS One
https://www.readbyqxmd.com/read/29741994/development-of-a-novel-explant-culture-method-for-the-isolation-of-mesenchymal-stem-cells-from-human-breast-tumor
#12
Koushan Sineh Sepehr, Alireza Razavi, Mohsen Saeidi, Majid Mossahebi-Mohammadi, Meghdad Abdollahpour-Alitappeh, Seyed Mahmoud Hashemi
BACKGROUND: Mesenchymal stem cells (MSCs) were isolated from various sources, including various types of tumors. However choosing an appropriate isolation method is an important step in obtaining cells with optimal quality and yield in companion with economical considerations. The purpose of this study was to isolate of more pure MSCs from human breast tumor tissue by a modified explant culture method. METHODS AND MATERIALS: The tumor tissues (n = 8) was cut into 1 to 3-mm cube-like pieces (explant)...
May 9, 2018: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/29741783/anti-angiogenic-effects-of-cd73-specific-sirna-loaded-nanoparticles-in-breast-cancer-bearing-mice
#13
Ghasem Ghalamfarsa, Ali Rastegari, Fatemeh Atyabi, Hadi Hassannia, Mohammad Hojjat-Farsangi, Amir Ghanbari, Enayat Anvari, Jamshid Mohammadi, Gholamreza Azizi, Ali Masjedi, Mehdi Yousefi, Bahman Yousefi, Jamshid Hadjati, Farhad Jadidi-Niaragh
CD73 facilitates tumor growth by upregulation of the adenosine (immunosuppressive factor) in the tumor microenvironment, however, its precise molecular mechanisms is not precisely understood. Regarding the importance of angiogenesis in tumor development and spreading, we decided to assign the anti-angiogenic effects of CD73 suppression. We used chitosan lactate (ChLa) nanoparticles (NPs) to deliver CD73-specific small interfering RNA (siRNA) into cancer cells. Our results showed that treatment of the 4T1 cells with CD73-specific siRNA-loaded NPs led to potent inhibition of cancer cell proliferation and cell cycle arrest, in vitro...
May 9, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29739946/notch-signaling-specifies-arterial-type-definitive-hemogenic-endothelium-from-human-pluripotent-stem-cells
#14
Gene I Uenishi, Ho Sun Jung, Akhilesh Kumar, Mi Ae Park, Brandon K Hadland, Ethan McLeod, Matthew Raymond, Oleg Moskvin, Catherine E Zimmerman, Derek J Theisen, Scott Swanson, Owen J Tamplin, Leonard I Zon, James A Thomson, Irwin D Bernstein, Igor I Slukvin
NOTCH signaling is required for the arterial specification and formation of hematopoietic stem cells (HSCs) and lympho-myeloid progenitors in the embryonic aorta-gonad-mesonephros region and extraembryonic vasculature from a distinct lineage of vascular endothelial cells with hemogenic potential. However, the role of NOTCH signaling in hemogenic endothelium (HE) specification from human pluripotent stem cell (hPSC) has not been studied. Here, using a chemically defined hPSC differentiation system combined with the use of DLL1-Fc and DAPT to manipulate NOTCH, we discover that NOTCH activation in hPSC-derived immature HE progenitors leads to formation of CD144+ CD43- CD73- DLL4+ Runx1 + 23-GFP+ arterial-type HE, which requires NOTCH signaling to undergo endothelial-to-hematopoietic transition and produce definitive lympho-myeloid and erythroid cells...
May 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29731776/potential-of-ipsc-derived-mesenchymal-stromal-cells-for-treating-periodontal-disease
#15
K Hynes, R Bright, V Marino, J Ng, P J Verma, S Gronthos, P M Bartold
Mesenchymal stromal cell-like populations have been derived from mouse-induced pluripotent stem cells (miPSC-MSC) with the capability for tissue regeneration. In this study, murine iPSC underwent differentiation towards an MSC-like immunophenotype. Stable miPSC-MSC cultures expressed the MSC-associated markers, CD73, CD105, and Sca-1, but lacked expression of the pluripotency marker, SSEA1, and hematopoietic markers, CD34 and CD45. Functionally, miPSC-MSC exhibited the potential for trilineage differentiation into osteoblasts, adipocytes, and chondrocytes and the capacity to suppress the proliferation of mitogen-activated splenocytes...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29731713/cytokine-induced-killer-cells-express-cd39-cd38-cd203a-cd73-ectoenzymes-and-p1-adenosinergic-receptors
#16
Alberto L Horenstein, Antonella Chillemi, Roberta Zini, Valeria Quarona, Nicoletta Bianchi, Rossella Manfredini, Roberto Gambari, Fabio Malavasi, Davide Ferrari
Cytokine-induced killer (CIK) cells, a heterogeneous T cell population obtained by in vitro differentiation of peripheral blood mononuclear cells (PBMC), represent a promising immunological approach in cancer. Numerous studies have explored the role of CD38, CD39, CD203a/PC-1, and CD73 in generating extracellular adenosine (ADO) and thus in shaping the tumor niche in favor of proliferation. The findings shown here reveal that CIK cells are able to produce extracellular ADO via traditional (CD39/CD73) and/or alternative (CD38/CD203a/CD73 or CD203a/CD73) pathways...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29725032/novel-evidence-that-extracellular-nucleotides-and-purinergic-signaling-induce-innate-immunity-mediated-mobilization-of-hematopoietic-stem-progenitor-cells
#17
Mateusz Adamiak, Kamila Bujko, Monika Cymer, Monika Plonka, Talita Glaser, Magda Kucia, Janina Ratajczak, Henning Ulrich, Ahmed Abdel-Latif, Mariusz Z Ratajczak
Pharmacological mobilization of hematopoietic stem progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB) is a result of mobilizing agent-induced "sterile inflammation" in the BM microenvironment due to complement cascade (ComC) activation. Here we provide evidence that ATP, as an extracellular nucleotide secreted in a pannexin-1-dependent manner from BM cells, triggers activation of the ComC and initiates the mobilization process. This process is augmented in a P2X7 receptor-dependent manner, and P2X7-KO mice are poor mobilizers...
March 30, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29720980/controlling-the-immune-suppressor-transcription-factors-and-micrornas-regulating-cd73-nt5e
#18
REVIEW
Theresa Kordaß, Wolfram Osen, Stefan B Eichmüller
The NT5E (CD73) molecule represents an ecto-5'-nucleotidase expressed on the cell surface of various cell types. Hydrolyzing extracellular adenosine monophosphate into adenosine and inorganic phosphate, NT5E performs numerous homeostatic functions in healthy organs and tissues. Importantly, NT5E can act as inhibitory immune checkpoint molecule, since free adenosine generated by NT5E inhibits cellular immune responses, thereby promoting immune escape of tumor cells. MicroRNAs (miRNAs) are small non-coding RNA molecules regulating gene expression on posttranscriptional level through binding to mRNAs, resulting in translational repression or degradation of the targeted mRNA molecule...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29714147/epithelial-in-vitro-differentiation-of-mesenchymal-stem-cells
#19
Alvaro Sierra-Sanchez, Alexandra Ordonez-Luque, Olga Espinosa-Ibanez, Antonio Ruiz-Garcia, Salvador Arias-Santiago
Mesenchymal stem cells or mesenchymal stromal cells (MSCs) are non-hematopoietic stromal cells that reside in and have been isolated from a variety of adult or fetal tissues such as adipose tissue, bone marrow and umbilical cord Wharton's jelly, among others. Because they are a heterogeneous population, International Society for Cellular Therapy has established 3 minimum criteria to characterize MSCs in vitro: i) adherence to plastic, ii) differentiation potential (osteogenic, chondrogenic and adipogenic lineages) and iii) expression of specific surface antigens (CD73+, CD90+, CD105+, CD34-, CD45-, CD11b-, CD14-, CD19-, CD79a-, HLA-DR-)...
May 1, 2018: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29688896/nox2-in-regulatory-t-cells-promotes-angiotensin-ii-induced-cardiovascular-remodeling
#20
Amber Emmerson, Silvia Cellone Trevelin, Heloise Mongue-Din, Pablo D Becker, Carla Ortiz, Lesley A Smyth, Qi Peng, Raul Elgueta, Greta Sawyer, Aleksandar Ivetic, Robert I Lechler, Giovanna Lombardi, Ajay M Shah
The superoxide-generating enzyme Nox2 contributes to hypertension and cardiovascular remodeling triggered by activation of the renin-angiotensin system. Multiple Nox2-expressing cells are implicated in angiotensin II (AngII)-induced pathophysiology, but the importance of Nox2 in leukocyte subsets is poorly understood. Here, we investigated the role of Nox2 in T cells, particularly Tregs. Mice globally deficient in Nox2 displayed increased numbers of Tregs in the heart at baseline whereas AngII-induced T-effector cell (Teffs) infiltration was inhibited...
April 24, 2018: Journal of Clinical Investigation
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