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Interleukin-15

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https://www.readbyqxmd.com/read/28639033/functional-restoration-of-cd56-bright-nk-cells-facilitates-immune-control-via-il-15-and-nkg2d-in-patients-under-antiviral-treatment-for-chronic-hepatitis-b
#1
Tao Chen, Lin Zhu, Aichao Shi, Lin Ding, Xiaoping Zhang, Zhenmin Tan, Wei Guo, Weiming Yan, Meifang Han, Jidong Jia, Xiaoping Luo, Detlef Schuppan, Qin Ning
BACKGROUND AND AIMS: Hepatitis B virus (HBV) is intrinsically immunogenic, with long-lasting immune control in many patients. However, the mechanisms and key cell types underlying effective immune control are incompletely understood. METHODS: We studied the restoration of natural killer (NK) cell numbers and function post antiviral treatment in 52 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who received telbivudine (LdT) for 48 weeks...
June 20, 2017: Hepatology International
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#2
Johan Mj Van den Bergh, Evelien Ljm Smits, Zwi N Berneman, Tim Ja Hutten, Hans De Reu, Viggo Fi Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DCs) is an appealing strategy to boost the GVT-response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28615524/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#3
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 4th 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)...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28602725/il15ra-is-required-for-osteoblast-function-and-bone-mineralization
#4
Emanuele Loro, Girish Ramaswamy, Abhishek Chandra, Wei-Ju Tseng, Manoj K Mishra, Eileen M Shore, Tejvir S Khurana
Interleukin-15 receptor alpha (IL15RA) is an important component of interleukin-15 (IL15) pro-inflammatory signaling. In addition, IL15 and IL15RA are present in the circulation and are detected in a variety of tissues where they influence physiological functions such as muscle contractility and overall metabolism. In the skeletal system, IL15RA was previously shown to be important for osteoclastogenesis. Little is known, however, about its role in osteoblast function and bone mineralization. In this study, we evaluated bone structural and mechanical properties of an Il15ra whole-body knockout mouse (Il15ra(-/-)) and used in vitro and bioinformatic analyses to understand the role IL15/IL15RA signaling on osteoblast function...
June 6, 2017: Bone
https://www.readbyqxmd.com/read/28581883/discovery-and-characterization-of-a-novel-humanized-anti-il-15-antibody-and-its-relevance-for-the-treatment-of-refractory-celiac-disease-and-eosinophilic-esophagitis
#5
Alain P Vicari, Alain M Schoepfer, Bertrand Meresse, Laurence Goffin, Olivier Léger, Soheila Josserand, Nicolas Guégan, Shida Yousefi, Alex Straumann, Nadine Cerf-Bensussan, Hans-Uwe Simon, Yolande Chvatchko
Interleukin-15 (IL-15) is a critical regulator of immune responses, especially at mucosal interfaces within the gastro-intestinal tract. Here, we describe the discovery and characterization of a humanized antibody to IL-15. Data from its epitope and mode of action, cell biology and primate pharmacology, as well as translational studies in human samples and in vivo proof-of-concept experiments in mouse models demonstrate the therapeutic potential of this new antibody targeting IL-15 for refractory celiac disease and eosinophilic esophagitis...
June 5, 2017: MAbs
https://www.readbyqxmd.com/read/28574833/new-interleukin-15-superagonist-il-15sa-significantly-enhances-graft-versus-tumor-activity
#6
Cavan P Bailey, Tulin Budak-Alpdogan, Christopher T Sauter, Michelle M Panis, Cihangir Buyukgoz, Emily K Jeng, Hing C Wong, Neal Flomenberg, Onder Alpdogan
Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535470/pharmacophore-guided-discovery-of-small-molecule-interleukin-15-inhibitors
#7
Barbara Żyżyńska-Granica, Bartosz Trzaskowski, Szymon Niewieczerzał, Sławomir Filipek, Oliwia Zegrocka-Stendel, Małgorzata Dutkiewicz, Piotr Krzeczyński, Magdalena Kowalewska, Katarzyna Koziak
Upregulation of interleukin 15 (IL-15) contributes directly i.a. to the development of inflammatory and autoimmune diseases. Selective blockade of IL-15 aimed to treat rheumatoid arthritis, psoriasis and other IL-15-related disorders has been recognized as an efficient therapeutic method. The aim of the study was to identify small molecules which would interact with IL-15 or its receptor IL-15Rα and inhibit the cytokine's activity. Based on the crystal structure of IL-15Rα·IL-15, we created pharmacophore models to screen the ZINC database of chemical compounds for potential IL-15 and IL-15Rα inhibitors...
May 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28490276/endometrial-stromal-and-epithelial-cells-exhibit-unique-aberrant-molecular-defects-in-patients-with-endometriosis
#8
Philip C Logan, Pamela Yango, Nam D Tran
CONTEXT: Endometriosis is a chronic inflammatory disease that causes pain and infertility in women of reproductive age. OBJECTIVE: To investigate the pathologic pathways in endometrial stromal and epithelial cells that contribute to the manifestation of endometriosis. DESIGN: In vitro cellular and molecular analyses of isolated eutopic endometrial stromal and epithelial cells. METHODS: Eutopic stromal and epithelial cells from endometriotic and normal patients were isolated by fluorescence-activated cell sorting for paired sibling RNA sequencing and microRNA microarray...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28470626/novel-adjuvant-for-immunization-against-tuberculosis-dna-vaccine-expressing-mycobacterium-tuberculosis-antigen-85a-and-interleukin-15-fusion-product-elicits-strong-immune-responses-in-mice
#9
Li Sun, Quan Yuan, Tianhua Xu, Li Yao, Jiangmin Feng, Jianfei Ma, Lining Wang, Changlong Lv, Danan Wang
OBJECTIVES: To investigate the potential of interleukin (IL)-15 as a novel adjuvant for Mycobacterium tuberculosis (Mtb) antigen 85A (Ag85A) vaccine. RESULTS: C57BL/6 mice were intramuscularly immunized three times with a plasmid expressing the Ag85A-IL-15 fusion protein (pcDNA3.1-Ag85A-IL-15), with the empty pcDNA3.1 vector and the pcDNA3.1-Ag85A as control. Mice vaccinated with pcDNA3.1-Ag85A-IL-15 generated more secretory IgA (sIgA) into their lung (209 ± 21 μg/ml) and acquired an enhanced serum IgG response to Ag85A...
May 3, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28408199/interleukin-15-and-cisplatin-co-encapsulated-thermosensitive-polypeptide-hydrogels-for-combined-immuno-chemotherapy
#10
Xilong Wu, Yundi Wu, Hongbo Ye, Shuangjiang Yu, Chaoliang He, Xuesi Chen
In situ-forming thermosensitive hydrogels based on poly(ethylene glycol)-poly(γ-ethyl-l-glutamate) diblock copolymers (mPEG-b-PELG) were prepared for the co-delivery of interleukin-15 (IL-15) and cisplatin (CDDP). The polypeptide-based hydrogels as local drug delivery carriers could reduce the systemic toxicity, degrade thoroughly within 3weeks after subcutaneous injection into rats and display an acceptable biocompatibility. When incubated with mouse melanoma B16 cells, only the CDDP-treated groups had significant effects on the S phase cell-cycle arrest in melanoma cells...
April 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28395334/natural-killer-cell-deficiency-alters-placental-development-in-rats
#11
Stephen J Renaud, Regan L Scott, Damayanti Chakraborty, Mohammad A K Rumi, Michael J Soares
Natural killer (NK) cells are the most prevalent leukocyte population in the uterus during early pregnancy. Natural killer cells contribute to uterine vascular (spiral artery) remodeling in preparation for the increased demand on these vessels later in pregnancy. A second wave of spiral artery modification is directed by invasive trophoblast cells. The significance of the initial wave of NK-cell-mediated vascular remodeling in species exhibiting deep trophoblast invasion such as humans and rats is not known...
January 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28391504/purification-of-inclusion-bodies-using-peg-precipitation-under-denaturing-conditions-to-produce-recombinant-therapeutic-proteins-from-escherichia-coli
#12
Huanhuan Chen, Ninghuan Li, Yueqing Xie, Hua Jiang, Xiaoyi Yang, Cedric Cagliero, Siwei Shi, Chencen Zhu, Han Luo, Junsheng Chen, Lei Zhang, Menglin Zhao, Lei Feng, Huili Lu, Jianwei Zhu
It has been documented that the purification of inclusion bodies from Escherichia coli by size exclusion chromatography (SEC) may benefit subsequent refolding and recovery of recombinant proteins. However, loading volume and the high cost of the column limits its application in large-scale manufacturing of biopharmaceutical proteins. We report a novel process using polyethylene glycol (PEG) precipitation under denaturing conditions to replace SEC for rapid purification of inclusion bodies containing recombinant therapeutic proteins...
July 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28379958/il-15-regulates-migration-invasion-angiogenesis-and-genes-associated-with-lipid-metabolism-and-inflammation-in-prostate-cancer
#13
Krizia Rohena-Rivera, María M Sánchez-Vázquez, Diana A Aponte-Colón, Ingrid S Forestier-Román, Mario E Quintero-Aguiló, Magaly Martínez-Ferrer
Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer. In the United States it is second leading cause of cancer related deaths in men. PCa is often treated via radical prostatectomy (RP). However, 15-30% of the patients develop biochemical recurrence (i.e. increased serum prostate specific antigen (PSA) levels). Interleukin-15 (IL-15) is a secreted cytokine found over expressed in patients with recurrence-free survival after RP. In our study, we aim to determine the role of IL-15 in PCa using in vitro and in vivo models, and gene expression analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28349952/nerve-regeneration-by-human-corneal-stromal-keratocytes-and-stromal-fibroblasts
#14
Gary Hin-Fai Yam, Geraint P Williams, Melina Setiawan, Nur Zahirah Binte M Yusoff, Xiao-Wen Lee, Hla Myint Htoon, Lei Zhou, Matthias Fuest, Jodhbir S Mehta
Laser refractive surgeries reshape corneal stroma to correct refractive errors, but unavoidably affect corneal nerves. Slow nerve regeneration and atypical neurite morphology cause desensitization and neuro-epitheliopathy. Following injury, surviving corneal stromal keratocytes (CSKs) are activated to stromal fibroblasts (SFs). How these two different cell types influence nerve regeneration is elusive. Our study evaluated the neuro-regulatory effects of human SFs versus CSKs derived from the same corneal stroma using an in vitro chick dorsal root ganglion model...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336113/effect-of-branched-chain-amino-acid-ratio-on-the-proliferation-differentiation-and-expression-levels-of-key-regulators-involved-in-protein-metabolism-of-myocytes
#15
Yehui Duan, Liming Zeng, Fengna Li, Wenlong Wang, Yinghui Li, Qiuping Guo, Yujiao Ji, Bi'e Tan, Yulong Yin
OBJECTIVES: Branched-chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile), and valine (Val), are key regulators of protein synthesis in muscle. The aim of this study was to investigate the effect of different BCAA ratios (Leu:Ile:Val) on the proliferation, differentiation, and expression levels of the regulators related to protein metabolism of C2 C12 myocytes. METHODS: Studies were conducted in C2C12 myocytes exposed to different BCAA ratios (Leu: Ile: Val = 0, 1:0...
April 2017: Nutrition
https://www.readbyqxmd.com/read/28291388/lymphoma-remissions-caused-by-anti-cd19-chimeric-antigen-receptor-t-cells-are-associated-with-high-serum-interleukin-15-levels
#16
James N Kochenderfer, Robert P T Somerville, Tangying Lu, Victoria Shi, Adrian Bot, John Rossi, Allen Xue, Stephanie L Goff, James C Yang, Richard M Sherry, Christopher A Klebanoff, Udai S Kammula, Marika Sherman, Arianne Perez, Constance M Yuan, Tatyana Feldman, Jonathan W Friedberg, Mark J Roschewski, Steven A Feldman, Lori McIntyre, Mary Ann Toomey, Steven A Rosenberg
Purpose T cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 (CAR-19) have potent activity against acute lymphoblastic leukemia, but fewer results supporting treatment of lymphoma with CAR-19 T cells have been published. Patients with lymphoma that is chemotherapy refractory or relapsed after autologous stem-cell transplantation have a grim prognosis, and new treatments for these patients are clearly needed. Chemotherapy administered before adoptive T-cell transfer has been shown to enhance the antimalignancy activity of adoptively transferred T cells...
June 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28274303/-recombinant-hbcag-promotes-secretion-of-il-15-in-myeloid-dendritic-cells-via-p38mapk-signaling-pathway
#17
Xin Zhang, Zhenhua Zhou, Man Li, Yating Gao, Xuehua Sun, Yueqiu Gao
Objective To study the mechanism by which recombinant human hepatitis B virus core antigen (rhHBcAg) induces interleukin-15 (IL-15) secretion in myeloid dendritic cells (mDCs). Methods Human peripheral blood monocytes were isolated from peripheral blood of healthy volunteers by Dynabeads Untouched Human monocytes kit. We obtained mDCs by culturing the monocytes in the presence of GM-CSF, IL-4 and TNF-α. In one group, mDCs were cultured in RPMI1640 and stimulated by rhHBcAg at the final concentration of 10 μg/mL for 1, 2, 3, 4, 5, 6 days...
March 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28251711/trophoblasts-regulate-natural-killer-cells-via-control-of-interleukin-15-receptor-signaling
#18
Seo Y Park, Sohyun Yun, Byung J Ryu, Ae R Han, Sung K Lee
PROBLEM: Trophoblasts are known to decrease natural killer (NK) cell cytotoxicity. However, little is known about the interaction between trophoblasts and NK cells during pregnancy. Interleukin-15 (IL-15) is essential for priming NK cells and maximizing their effector functions. We investigated whether trophoblasts regulate NK cell activation via IL-15/IL-2 receptor and its signaling pathways. METHOD OF STUDY: Natural killer-92 cells were primed with human first-trimester trophoblast cells (Sw...
March 2, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28246360/multiple-histone-lysine-methyltransferases-are-required-for-the-establishment-and-maintenance-of-hiv-1-latency
#19
Kien Nguyen, Biswajit Das, Curtis Dobrowolski, Jonathan Karn
We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28181907/the-role-of-interleukin-15-in-neoplasia
#20
Małgorzata Chłopek, Artur Kowalik, Stanisław Góźdź, Katarzyna Koziak
Interleukin 15 is a pleiotropic cytokine of the four α helix bundle family. Binding to a heterotrimeric receptor complex, which consists of a unique, high affinity IL‑15Rα‑chain and IL-2/IL-15Rβ and IL‑2Rγ chains, IL‑15 activates signaling pathways leading to activation and proliferation of T and B cells, as well as natural killer cells. At the same time, IL‑15 protects effector cells from T regulatory cells and does not induce immune tolerance. The significant regulatory action of IL‑15 on the immune system provides new opportunities for development of anti‑cancer therapies...
January 10, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
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