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Yanqin Sun, Jiali Long, Yuting Yin, Hongmei Li, Enping Jiang, Chao Zeng, Wei Zhu
We build the latent membrane protein gene LMP2A and GM-CSF gene fusion gene (CSF2A), and discuss how CSF2A fusion protein influenced proliferation and apoptosis of EBV+ tumor cells. RT-PCR method was used to amplify LMP2A gene and GM-CSF gene fragments respectively, according to the principle of overlap extension in the coding (Gly4Ser)3 polypeptide gene fragments of DNA restructured under the connection. CSF2A gene could be connected with pIRES2-eGFP vector by recombinant DNA technology, and identified by enzyme electrophoresis analysis and DNA sequencing...
June 13, 2018: Journal of Medical Virology
Jorge Gallego-Valle, Verónica Astrid Pérez-Fernández, Rafael Correa-Rocha, Marjorie Pion
Regulatory B cells (Bregs) participate in auto-tolerance maintenance and immune homeostasis. Despite their impact on many diseases and due to the difficulty to define them, knowledge about their origin and their physiological inducers is still unclear. The incomplete understanding about the generation of Bregs and their limited numbers in periphery make it difficult to develop Breg-based therapy. Therefore, identifying factors that promote their development would allow their ex-vivo production in order to create new immunotherapy...
June 12, 2018: International Journal of Molecular Sciences
Elena R Chernykh, Ludmila V Sakhno, Ekaterina Ya Shevela, Marina A Tikhonova, Natalia A Khonina, Alexandr A Ostanin
The engulfment of apoptotic cells by monocytes and unprimed macrophages results in M2 polarization. In the current study, we investigated whether apoptotic cells influence the phenotypic and functional characteristics of GM-CSF-differentiated human macrophages (GM-Mφ). Our results demonstrate that GM-Mφ preincubated with apoptotic neutrophils (GM-MφNeu ) show significantly increased expression of CD206 and FasL and decreased capacity to stimulate allogeneic T-cell proliferation thus adopting M2 features...
June 7, 2018: Cellular Immunology
Ryutaro Iwabuchi, Shota Ikeno, Mie Kobayashi-Ishihara, Haruko Takeyama, Manabu Ato, Yasuko Tsunetsugu-Yokota, Kazutaka Terahara
Two cytokines, fms-related tyrosine kinase 3 ligand (Flt3-L) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are considered to be the essential regulators of dendritic cell (DC) development in vivo . However, the combined effect of Flt3-L and GM-CSF on human DCs has not been evaluated in vivo . In this study, we, therefore, aimed at evaluating this using a humanized mouse model. Humanized non-obese diabetic/SCID/Jak3null (hNOJ) mice were constructed by transplanting hematopoietic stem cells from human umbilical cord blood into newborn NOJ mice, and in vivo transfection (IVT) was performed by hydrodynamic injection-mediated gene delivery using plasmids encoding human Flt3-L and GM-CSF...
2018: Frontiers in Immunology
Jessica McHugh
No abstract text is available yet for this article.
June 11, 2018: Nature Reviews. Rheumatology
Xiao-Ran Yu, Qiao-Sheng Wen, Yi Xiao, Rui Tang, Fu-Xi Li, Wen-Feng Shao, Yan-Lin Yu, Jing-Bo Xiong
OBJECTIVE: To study if programmed death-ligand 1 (PL-L1) expression in breast cancer cell activates PD-L1/PD-1 pathway in dendritic cells to inhibit dendritic cell maturation. METHODS: Human monocytes were induced to differentiate into immature dendritic cells using GM-CSF and IL-4, and further to mature dendritic cells using TNF-α. PD-L1-expressing breast cancer cell line MDA-MB-231 was co-cultured in contact with the dendritic cells to observe the effects of the breast cancer cells on the maturation of the dendritic cells...
May 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Rebecca A Drummond, Fatema Tuz Zahra, Mukil Natarajan, Muthulekha Swamydas, Amy P Hsu, L Joseph Wheat, Christina Gavino, Donald C Vinh, Steven H Holland, Constantinos M Mikelis, Michail S Lionakis
CARD9 deficiency is associated with life-threatening fungal infections of the CNS. This work shows that the H-RAS/RASGRF1/ERK pathway is intact in the c.170G>A (p.R57H) CARD9 missense mutation, a finding that correlates with the clinical outcome of GM-CSF therapy.
June 8, 2018: Journal of Allergy and Clinical Immunology
Kevin C Conlon, Milos D Miljkovic, Thomas A Waldmann
Cytokines are major regulators of innate and adaptive immunity that enable cells of the immune system to communicate over short distances. Cytokine therapy to activate the immune system of cancer patients has been an important treatment modality and continues to be a key contributor to current clinical cancer research. Interferon alpha (IFNα) is approved for adjuvant treatment of completely resected high-risk melanoma patients and several refractory malignancies. High-dose interleukin-2 (HDIL-2) is approved for treatment of metastatic renal cell cancer and melanoma, but both agents are currently less commonly used with the development of newer agents...
June 11, 2018: Journal of Interferon & Cytokine Research
Ricardo Villares, Gabriel Criado, Yasmina Juarranz, Mercedes Lopez-Santalla, Eva M García-Cuesta, José M Rodríguez-Frade, Javier Leceta, Pilar Lucas, José Luis Pablos, Carlos Martínez-A, Marina I Garin, Rosa P Gomariz, Mario Mellado
Evidence indicates an intimate connection between the neuroendocrine and the immune systems. A number of in vitro and in vivo studies have demonstrated growth hormone (GH) involvement in immune regulation. The GH receptor is expressed by several leukocyte subpopulations, and GH modulates immune cell proliferation and activity. Here, we found that sustained GH expression protected against collagen-induced arthritis (CIA); in GH-transgenic C57BL/6 (GHTg) mice, disease onset was delayed, and its overall severity was decreased...
2018: Frontiers in Immunology
Tamirys Simão Pimenta, Natalie Ferreira Chaves, Ana Paula Drummond Rodrigues, Cristovam Wanderley Picanço Diniz, Renato Augusto DaMatta, José Antônio Picanço Diniz Junior
In vitro studies have demonstrated that GM-CSF in combination with other stimulatory factors induces a microbicidal response that control T. gondii infection. We assessed whether GM-CSF alone can control T. gondiireplication in murine microglial cultures. Microglia were collected and cultured with or without GM-CSF and the half of each group was infected with T. gondii. We determined the T. gondii infectivity, cytokines levels, NO and superoxide detection.GM-CSF alone primes microglia, which after infection induces the production of TNF-α and IL-6, leading to NO and superoxide production, without any stimulus from IL-12p70 and IFN-γ...
June 7, 2018: Microbes and Infection
Young-Jin Kim, Ji Young Lee, Hyun-Ju Kim, Do-Hoon Kim, Tae Hee Lee, Mi Suk Kang, Wansu Park
The dry root of Angelica sinensis (Oliv.) Diels, also known as “female ginseng”, is a popular herbal drug amongst women, used to treat a variety of health issues and cardiovascular diseases. The aim of this study is to evaluate the detailed molecular mechanism for anti-inflammatory effects of Angelica sinensis root water extract (ASW). The anti-inflammatory effect of ASW on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages was evaluated by the tetrazolium-based colorimetric assay (MTT), Griess reagent assay, multiplex cytokine assay, real time reverse transcription polymerase chain reaction (RT-PCR), and Fluo-4 calcium assay...
May 21, 2018: Nutrients
Elizabeth E Puscheck, Alan Bolnick, Awoniyi Awonuga, Yu Yang, Mohammed Abdulhasan, Quanwen Li, Eric Secor, Erica Louden, Maik Hüttemann, Daniel A Rappolee
Here we examine recent evidence suggesting that many drugs and diet supplements (DS), experimental AMP-activated protein kinase (AMPK) agonists as well as energy-depleting stress, lead to decreases in anabolism, growth or proliferation, and potency of cultured oocytes, embryos, and stem cells in an AMPK-dependent manner. Surprising data for DS and drugs that have some activity as AMPK agonists in in vitro experiments show possible toxicity. This needs to be balanced against a preponderance of evidence in vivo that these drugs and DS are beneficial for reproduction...
June 7, 2018: Journal of Assisted Reproduction and Genetics
Sulayman Benmerzoug, Fabio Vitarelli Marinho, Stéphanie Rose, Claire Mackowiak, David Gosset, Delphine Sedda, Emeline Poisson, Catherine Uyttenhove, Jacques Van Snick, Muazzam Jacobs, Irene Garcia, Bernhard Ryffel, Valerie F J Quesniaux
Host directed immunomodulation represents potential new adjuvant therapies in infectious diseases such as tuberculosis. Major cytokines like TNFα exert a multifold role in host control of mycobacterial infections. GM-CSF and its receptor are over-expressed during acute M. tuberculosis infection and we asked how GM-CSF neutralization might affect host response, both in immunocompetent and in immunocompromised TNFα-deficient mice. GM-CSF neutralizing antibodies, at a dose effectively preventing acute lung inflammation, did not affect M...
June 5, 2018: Scientific Reports
Amy T Hsu, Tanya J Lupancu, Ming-Chin Lee, Andrew J Fleetwood, Andrew D Cook, John A Hamilton, Adrian Achuthan
Interleukin 4 (IL4) is generally viewed as a Th2 cytokine capable of polarizing macrophages into an anti-inflammatory phenotype, while granulocyte macrophage-colony stimulating factor (GM-CSF), on the other hand, is often viewed as a proinflammatory cytokine with part of this function due to its action on monocytes/macrophages. Paradoxically, these two cytokines act additively to enhance in vitro the differentiation of dendritic cells from precursors such as monocytes. One upregulated marker of an IL4-polarized M2 macrophage is the chemokine (C-C motif) ligand 17 (CCL17), which we have recently reported to be induced by GM-CSF in monocytes/macrophages in an interferon regulatory factor 4 (IRF4)-dependent manner...
June 5, 2018: Journal of Biological Chemistry
Patrícia A F Ribeiro, Daniel S Dias, Daniela P Lage, Lourena E Costa, Vívian T Martins, Grasiele S V Tavares, Débora V C Mendonça, Mariana P Lima, Jamil S Oliveira, Bethina T Steiner, Ricardo A Machado-de-Ávila, Bruno M Roatt, Miguel A Chávez-Fumagalli, Daniel Menezes-Souza, Mariana C Duarte, Antonio L Teixeira, Eduardo A F Coelho
Visceral leishmaniasis (VL) is a fatal disease when acute and untreated. The treatment against this disease is long and presents toxicity and/or high costs. Moreover, parasite resistance has been increasing. Therefore, alternative control measures to avoid the spread of disease should be considered. It is accepted that the development of the T helper (Th)1 immune response, based on the production of pro-inflammatory cytokines, is required for the control of parasites. Although recombinant protein-based vaccines have been tested against VL, they require supplementation with immune adjuvants...
May 29, 2018: Cellular Immunology
Miriam C N Eller, Karina P Vergani, Beatriz M Saraiva-Romanholo, Leila Antonangelo, Claudio Leone, Joaquim C Rodrigues
BACKGROUND: The phenotypes and endotypes of severe therapy-resistant asthma (STRA) have not been fully elucidated in children. The aim of the present study was to investigate inflammatory markers in the induced sputum of children with STRA and to compare them with those present in a group of children who achieved control. METHODS: A prospective cohort of children (6-18 years of age) diagnosed with severe asthma (GINA criteria) who had undergone treatment for at least 6 months was comprehensively followed for 3 months...
June 5, 2018: Pediatric Pulmonology
Jennifer A Juno, Jillian L M Waruk, Kathleen M Wragg, Christine Mesa, Carmen Lopez, Joe Bueti, Stephen J Kent, T Blake Ball, Sandra A Kiazyk
Background: End-stage renal disease (ESRD) is associated with an increased susceptibility to infectious diseases, including infection with Mycobacterium tuberculosis (Mtb) . Mucosal-associated invariant T (MAIT) cells recognize vitamin B metabolites produced by many bacterial species, including Mtb, and may play an important role in providing protective immunity against tuberculosis infection in the lung. To date, little is known about MAIT cell frequency, phenotype, or function in ESRD patients...
2018: Frontiers in Immunology
Sjoerd T T Schetters, Laura J W Kruijssen, Matheus H W Crommentuijn, Hakan Kalay, Jordi Ochando, Joke M M den Haan, Juan J Garcia-Vallejo, Yvette van Kooyk
The efficacy of vaccination studies aimed at targeting antigens to human DC-SIGN (hDC-SIGN) have been notoriously difficult to study in vivo , as eight dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) homologs have been described in mice. CD209a/SIGNR5 has been coined as the mouse DC-SIGN (mDC-SIGN) ortholog, based on its expression and location in the genome. Nonetheless, which properties of hDC-SIGN are covered by mDC-SIGN is poorly investigated. One of the most important functions of DC-SIGN is the induction of adaptive immunity...
2018: Frontiers in Immunology
Ali Danesh, Heather C Inglis, Mohamed Abdel-Mohsen, Xutao Deng, Avril Adelman, Kenneth B Schechtman, John W Heitman, Ryan Vilardi, Avani Shah, Sheila M Keating, Mitchell J Cohen, Evan S Jacobs, Satish K Pillai, Jacques Lacroix, Philip C Spinella, Philip J Norris
To understand how extracellular vesicle (EV) subtypes differentially activate monocytes, a series of in vitro studies were performed. We found that plasma-EVs biased monocytes toward an M1 profile. Culturing monocytes with granulocyte-, monocyte-, and endothelial-EVs induced several pro-inflammatory cytokines. By contrast, platelet-EVs induced TGF-β and GM-CSF, and red blood cell (RBC)-EVs did not activate monocytes in vitro . The scavenger receptor CD36 was important for binding of RBC-EVs to monocytes, while blockade of CD36, CD163, CD206, TLR1, TLR2, and TLR4 did not affect binding of plasma-EVs to monocytes in vitro ...
2018: Frontiers in Immunology
Markus D Lacher, Gerhard Bauer, Brian Fury, Sanne Graeve, Emily L Fledderman, Tye D Petrie, Dane P Coleal-Bergum, Tia Hackett, Nicholas H Perotti, Ying Y Kong, William W Kwok, Joseph P Wagner, Charles L Wiseman, William V Williams
Targeted cancer immunotherapy with irradiated, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting, allogeneic cancer cell lines has been an effective approach to reduce tumor burden in several patients. It is generally assumed that to be effective, these cell lines need to express immunogenic antigens coexpressed in patient tumor cells, and antigen-presenting cells need to take up such antigens then present them to patient T cells. We have previously reported that, in a phase I pilot study (ClinicalTrials...
2018: Frontiers in Immunology
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