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Interleukin-15

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https://www.readbyqxmd.com/read/29308327/enhancement-of-antibody-dependent-cellular-cytotoxicity-of-cetuximab-by-a-chimeric-protein-encompassing-interleukin-15
#1
Maria Carmen Ochoa, Luna Minute, Ascensión López, Elisabeth Pérez-Ruiz, Celia Gomar, Marcos Vasquez, Susana Inoges, Iñaki Etxeberria, Inmaculada Rodriguez, Saray Garasa, Jan-Peter Andreas Mayer, Peter Wirtz, Ignacio Melero, Pedro Berraondo
Enhancement of antibody-dependent cellular cytotoxicity (ADCC) may potentiate the antitumor efficacy of tumor-targeted monoclonal antibodies. Increasing the numbers and antitumor activity of NK cells is a promising strategy to maximize the ADCC of standard-of-care tumor-targeted antibodies. For this purpose, we have preclinically tested a recombinant chimeric protein encompassing the sushi domain of the IL15Rα, IL-15, and apolipoprotein A-I (Sushi-IL15-Apo) as produced in CHO cells. The size-exclusion purified monomeric fraction of this chimeric protein was stable and retained the IL-15 and the sushi domain bioactivity as measured by CTLL-2 and Mo-7e cell proliferation and STAT5 phosphorylation in freshly isolated human NK and CD8+ T cells...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29296227/effects-of-three-il-15-variants-on-nci-h446-cell-proliferation-and-expression-of-cell-cycle-regulatory-molecules
#2
Jun-Ying Ding, Zhi-Hua Wang, Zheng-Zheng Zhang, Xu-Ran Cui, Yan-Ying Hong, Qing-Quan Liu
Interleukin 15 (IL-15) is a cytokine exhibiting antitumor characteristic similar to that of IL-2. However, in human tissues and cells, IL-15 expression and secretion is very limited, suggesting IL-15 functions mainly intracellularly. In the present study, we assessed the effects of transfecting NCI-H446 small cell lung cancer cells with genes encoding three IL-15 variants: prototypical IL-15, mature IL-15 peptide, and modified IL-15 in which the IL-2 signal peptide is substituted for the native signal peptide...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29286001/environmental-stimuli-shape-microglial-plasticity-in-glioma
#3
Stefano Garofalo, Alessandra Porzia, Fabrizio Mainiero, Silvia Di Angelantonio, Barbara Cortese, Bernadette Basilico, Francesca Pagani, Giorgio Cignitti, Giuseppina Chece, Roberta Maggio, Eve Tremblay, Julie Savage, Kanchan Bisht, Vincenzo Esposito, Giovanni Bernardini, Thomas Seyfried, Jakub Mieczkowski, Karolina Stepniak, Bozena Kaminska, Angela Santoni, Cristina Limatola
In glioma, microglia and infiltrating macrophages are exposed to factors that force them to produce cytokines and chemokines, contributing to tumor growth and maintaining a pro-tumorigenic, immunosuppressed microenvironment. We demonstrate that housing glioma-bearing mice in enriched environment (EE) reverts the immunosuppressive phenotype of infiltrating myeloid cells, by modulating inflammatory gene expression. Under these conditions, branching and patrolling activity of myeloid cells is increased, and their phagocytic activity is promoted...
December 29, 2017: ELife
https://www.readbyqxmd.com/read/29222435/long-term-maintenance-of-peripheral-blood-derived-human-nk-cells-in-a-novel-human-il-15-transgenic-nog-mouse
#4
Ikumi Katano, Chiyoko Nishime, Ryoji Ito, Tsutomu Kamisako, Takuma Mizusawa, Yuyo Ka, Tomoyuki Ogura, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi
We generated a novel mouse strain expressing transgenic human interleukin-15 (IL-15) using the severe immunodeficient NOD/Shi-scid-IL-2Rγ null (NOG) mouse genetic background (NOG-IL-15 Tg). Human natural killer (NK) cells, purified from the peripheral blood (hu-PB-NK) of normal healthy donors, proliferated when transferred into NOG-IL-15 Tg mice. In addition, the cell number increased, and the hu-PB-NK cells persisted for 3 months without signs of xenogeneic graft versus host diseases (xGVHD). These in vivo-expanded hu-PB-NK cells maintained the original expression patterns of various surface antigens, including NK receptors and killer cell immunoglobulin-like receptor (KIR) molecules...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29203590/a-first-in-human-phase-1-study-of-subcutaneous-outpatient-recombinant-human-il-15-rhil-15-in-adults-with-advanced-solid-tumors
#5
Jeffrey S Miller, Chihiro Morishima, Douglas G McNeel, Manish R Patel, Holbrook E Kohrt, John A Thompson, Paul M Sondel, Heather A Wakelee, Mary L Disis, Judith C Kaiser, Martin A Cheever, Howard Streicher, Stephen P Creekmore, Thomas A Waldmann, Kevin C Conlon
PURPOSE: Preclinical data established Interleukin-15 as a homeostatic factor and powerful stimulator of NK and CD8+ T cell function, the basis for clinical testing. EXPERIMENTAL DESIGN: A first-in-human outpatient phase I dose escalation trial of subcutaneous (SC) rhIL-15 was conducted in refractory solid tumor cancer patients. Therapy consisted of daily (Monday - Friday) SC injections of rhIL-15 for two consecutive weeks (10 total doses/cycle). Clinical response was assessed by RECIST...
December 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29180399/diminished-microrna-29b-level-is-associated-with-brd4-mediated-activation-of-oncogenes-in-cutaneous-t-cell-lymphoma
#6
Rebecca Kohnken, Jing Wen, Bethany Mundy-Bosse, Kathleen McConnell, Ashleigh Keiter, Leah Grinshpun, Alex Hartlage, Max Yano, Betina McNeil, Nitin Chakravarti, Basem William, James E Bradner, Michael A Caligiuri, Pierluigi Porcu, Anjali Mishra
MicroRNA dysregulation is a hallmark of cutaneous T-cell lymphoma (CTCL), a uniformly fatal malignancy of skin-homing CD4+ T-cells for which there are few effective therapies. The role of microRNAs (miRs) in controlling epigenetic modifier-dependent transcriptional regulation in CTCL is unknown. In this study, we characterize a novel miR dysregulation contributing to overexpression of epigenetic reader bromodomain-containing protein 4 (BRD4). Using patient CD4+ T-cells, we show diminished levels of miR-29b compared to healthy donor cells...
November 27, 2017: Blood
https://www.readbyqxmd.com/read/29177585/the-role-of-exercise-induced-myokines-in-regulating-metabolism
#7
REVIEW
Joo Young Huh
Exercise has beneficial effects in ameliorating metabolic disorders, and a combined therapeutic regimen of regular exercise and pharmaceutical treatment is often recommended. Exercise biology is complex and it involves various metabolic and molecular changes that translate into changes in substrate utilization, enzyme activation, and alternatively, improvement in exercise performance. Besides the effect of exercise on muscle metabolism, it has recently been discovered that contracting muscle can induce secretion of molecules called myokines...
November 25, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29168191/genetic-variants-in-il15-promoter-affect-transcription-activity-and-intramuscular-fat-deposition-in-longissimus-dorsi-muscle-of-pigs
#8
D He, Z Jiang, Y Tian, H Han, M Xia, W Wei, L Zhang, J Chen
Intramuscular fat (IMF) content is a key aspect of pork quality. Elucidation of intramuscular adipocyte regulation mechanisms is important for improving IMF content. Intramuscular adipocytes are dispersed among muscle fibers, so they are inclined to be affected by muscle-derived factors. Interleukin-15 is a major muscle-secreted factor. In this study, the genetic and physiological impacts of IL15 on adipogenesis is investigated. The promoter region of IL15 was scanned by comparative sequencing using two DNA pools of high- and low-IMF individuals...
November 22, 2017: Animal Genetics
https://www.readbyqxmd.com/read/29110110/changes-and-clinical-significance-of-cd8-cd122-t-cells-in-the-peripheral-blood-of-patients-with-ankylosing-spondylitis
#9
Renfang Han, Xiao Yang, Mengya Chen, Xu Zhang, Yaping Yuan, Xingxing Hu, Mengmeng Wang, Rui Liu, Yubo Ma, Jiajia Yang, Shengqian Xu, Zongwen Shuai, Shanqun Jiang, Faming Pan
The aim of our study was to explore the relationship between circulating T cells and ankylosing spondylitis (AS) and to find the role of the CD8+CD122+ T cells in the pathogenesis and progression of AS. With the method of case-control design, flow cytometry was performed to quantitatively determine the percentage of circulating CD8(+)CD122(+) T cells in peripheral blood mononuclear cells from established AS patients and age- and gender-matched healthy controls. Serum levels of inflammatory cytokines like interleukin-2, interleukin-10, interleukin-15, TGF-β1, and TNF-ɑ were detected by enzyme-linked immunosorbent assay...
November 6, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/29105654/critical-functions-for-stat5-tetramers-in-the-maturation-and-survival-of-natural-killer-cells
#10
Jian-Xin Lin, Ning Du, Peng Li, Majid Kazemian, Tesfay Gebregiorgis, Rosanne Spolski, Warren J Leonard
Interleukin-15 (IL-15) is essential for the development and maintenance of natural killer (NK) cells. IL-15 activates STAT5 proteins, which can form dimers or tetramers. We previously found that NK cell numbers are decreased in Stat5a-Stat5b tetramer-deficient double knockin (DKI) mice, but the mechanism was not investigated. Here we show that STAT5 dimers are sufficient for NK cell development, whereas STAT5 tetramers mediate NK cell maturation and the expression of maturation-associated genes. Unlike the defective proliferation of Stat5 DKI CD8(+) T cells, Stat5 DKI NK cells have normal proliferation to IL-15 but are susceptible to death upon cytokine withdrawal, with lower Bcl2 and increased active caspases...
November 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29097254/interleukin-15-derived-from-guanylin-gc-c-expressing-macrophages-inhibits-fatty-acid-synthase-in-adipocytes
#11
Sayaka Akieda-Asai, Takanori Ida, Mikiya Miyazato, Kenji Kangawa, Yukari Date
Recently we found that guanylin (Gn) and its receptor, guanylyl cyclase C (GC-C), are uniquely expressed in the mesenteric macrophages of some diet-resistant rats and that double-transgenic (dTg) rats overexpressing Gn and GC-C in macrophages demonstrate reduced fatty acid synthase and fat accumulation in fat tissue even when fed a high-fat diet (HFD). Lipid accumulation and fatty acid synthase mRNA levels in cocultured dTg rat adipocytes and macrophages were reduced compared with those in adipocytes cultured with WT rat macrophages...
October 31, 2017: Peptides
https://www.readbyqxmd.com/read/29078283/humanized-mouse-model-supports-development-function-and-tissue-residency-of-human-natural-killer-cells
#12
Dietmar Herndler-Brandstetter, Liang Shan, Yi Yao, Carmen Stecher, Valerie Plajer, Melanie Lietzenmayer, Till Strowig, Marcel R de Zoete, Noah W Palm, Jie Chen, Catherine A Blish, Davor Frleta, Cagan Gurer, Lynn E Macdonald, Andrew J Murphy, George D Yancopoulos, Ruth R Montgomery, Richard A Flavell
Immunodeficient mice reconstituted with a human immune system represent a promising tool for translational research as they may allow modeling and therapy of human diseases in vivo. However, insufficient development and function of human natural killer (NK) cells and T cell subsets limit the applicability of humanized mice for studying cancer biology and therapy. Here, we describe a human interleukin 15 (IL15) and human signal regulatory protein alpha (SIRPA) knock-in mouse on a Rag2-/- Il2rg-/- background (SRG-15)...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29071664/the-relationship-between-plasma-interleukin-15-levels-and-sarcopenia-in-outpatient-older-people
#13
Ahmet Yalcin, Kamile Silay, Ahmet Rifat Balik, Gamze Avcioğlu, Almila Senat Aydin
BACKGROUND AND AIM: Sarcopenia is a geriatric syndrome in which there is a decrease in muscle mass, muscle strength, and muscle function. Interleukin-15 (IL-15), a myokine released by skeletal muscle, has effects on both muscle and adipose tissue. We evaluated the relationship between plasma IL-15 level and sarcopenia. METHODS: We evaluated a total of 160 outpatient older people, and 80 of whom had sarcopenia. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People criteria...
October 25, 2017: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/29051779/childhood-maltreatment-and-inflammation-among-pregnant-women-with-gestational-diabetes-mellitus-a-pilot-study
#14
Margaret Bublitz, Suzanne De La Monte, Susan Martin, Lucia Larson, Ghada Bourjeily
BACKGROUND: Women with childhood maltreatment histories are at increased risk for adverse birth outcomes. Mechanisms explaining this link are poorly understood. Past research is limited by sampling pregnant women at low risk for adverse maternal and neonatal outcomes. METHODS: This pilot study was a secondary data analysis of 24 women with gestational diabetes mellitus; 17% of the sample also reported a maltreatment history. Women provided a blood sample to measure inflammatory cytokines and insulin resistance, and saliva samples to measure diurnal cortisol...
September 2017: Obstetric Medicine
https://www.readbyqxmd.com/read/29030501/enzymatic-synthesis-of-core-2-o-glycans-governs-the-tissue-trafficking-potential-of-memory-cd8-t-cells
#15
Jossef F Osborn, Jana L Mooster, Samuel J Hobbs, Michael W Munks, Conrad Barry, John T Harty, Ann B Hill, Jeffrey C Nolz
Trafficking of memory CD8(+) T cells out of the circulation is essential to provide protective immunity against intracellular pathogens in nonlymphoid tissues. However, the molecular mechanisms that dictate the trafficking potential of diverse memory CD8(+) T cell populations are not completely defined. We show that after infection or inflammatory challenge, central memory (TCM) CD8(+) T cells rapidly traffic into nonlymphoid tissues, whereas most effector memory cells remain in the circulation. Furthermore, we demonstrate that cellular migration of memory CD8(+) T cells into nonlymphoid tissues is driven by interleukin-15 (IL-15)-stimulated enzymatic synthesis of core 2 O-glycans, which generates functional ligands for E- and P-selectins...
October 13, 2017: Science Immunology
https://www.readbyqxmd.com/read/29023581/activating-and-inhibitory-receptors-on-natural-killer-cells-in-patients-with-systemic-lupus-erythematosis-regulation-with-interleukin-15
#16
Syh-Jae Lin, Ming-Ling Kuo, Hsiu-Shan Hsiao, Pei-Tzu Lee, Ji-Yih Chen, Jing-Long Huang
Natural killer (NK) cells may play an important role in the pathogenesis of SLE. Interleukin(IL)-15, an NK-enhancing cytokine, is over-expressed in SLE patients. In the present study, we examined the effect of IL-15 on NK cytotoxicity of SLE patients, and the expression of various activating and inhibitory NK receptors on NK cells from SLE patients in relation to disease activity. We also sought to determine how IL-15 would affect the NK receptor expression on NK cells from SLE patients. PBMCs were collected from 88 SLE patients with inactive disease activity (SLEDAI score<6) and active disease activity (SLEDAI score≥6), 26 age-matched healthy adults were used as controls...
2017: PloS One
https://www.readbyqxmd.com/read/28986344/nk-cell-recovery-after-haploidentical-hsct-with-post-transplant-cyclophosphamide-dynamics-and-clinical-implications
#17
Antonio Russo, Giacomo Oliveira, Sofia Berglund, Raffaella Greco, Valentina Gambacorta, Nicoletta Cieri, Cristina Toffalori, Laura Zito, Francesca Lorentino, Simona Piemontese, Mara Morelli, Fabio Giglio, Andrea Assanelli, Maria Teresa Lupo Stanghellini, Chiara Bonini, Jacopo Peccatori, Fabio Ciceri, Leo Luznik, Luca Vago
The use of post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis has revolutionized haploidentical HSCT, allowing safe infusion of unmanipulated T cell-replete grafts. PT-Cy selectively eliminates proliferating alloreactive T cells, but whether and how it affects NK cells and their alloreactivity is largely unknown. Here we characterized NK cell dynamics in 17 patients who received unmanipulated haploidentical grafts, containing high numbers of mature NK cells, according to PT-Cy-based protocols in two independent centers...
October 6, 2017: Blood
https://www.readbyqxmd.com/read/28915646/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#18
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4(th) leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28827115/effect-of-il15-rs10833-and-scarb1-rs10846744-on-virologic-responses-in-chronic-hepatitis-c-patients-treated-with-pegylated-interferon-%C3%AE-and-ribavirin
#19
Sahar Sadeghi, Mehdi Davari, Esmaeil Asli, Safoora Gharibzadeh, Farzam Vaziri, Fatemeh Rahimi Jamnani, Abolfazl Fateh, Seyed Davar Siadat
The scavenger receptor type B class I (SCARBI) is known to be involved in the entry of hepatitis C virus (HCV) into the host, while interleukin-15 (IL15) is an important cytokine in both the innate and acquired immune responses against HCV infection. We investigated the association of IL15 rs10833 or SCARB1 rs10846744 polymorphisms with treatment responses in patients with chronic HCV (CHC). SCARB1 rs10846744 and IL15 rs10833 were identified in 365 treatment-naïve CHC patients through genotyping by TaqMan® Real-Time PCR and PCR-restriction fragment length polymorphism (RFLP), respectively...
September 30, 2017: Gene
https://www.readbyqxmd.com/read/28816622/obtention-and-characterization-of-the-recombinant-simian-interleukin-15-in-escherichia-coli-for-the-preclinical-assessment-of-an-il-15-based-therapeutic-vaccine
#20
Yunier Rodríguez-Álvarez, Klaudia Martínez-Cordovez, Alexey Llopiz-Arzuaga, Yassel Ramos-Gómez, Vladimir Besada-Pérez, Dayana García-Lines, Alicia Santos-Savio
Recombinant simian IL-15 (siIL-15) was obtained for the preclinical assessment of an anti-human IL-15 vaccine. For this purpose, the cDNA from peripheral blood mononuclear cells of a Macaca fascicularis monkey was cloned into a pIL-2 vector. The siIL-15 was expressed in Escherichia coli strain W3110 as an insoluble protein which accounted for 13% of the total cellular proteins. Inclusion bodies were solubilized in an 8 M urea solution, which was purified by ion exchange and reverse phase chromatography up to 92% purity...
August 17, 2017: Preparative Biochemistry & Biotechnology
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