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Shantaé M Thornton, James E Krolopp, Marcia J Abbott
Molecular mediators of metabolic processes, to increase energy expenditure, have become a focus for therapies of obesity. The discovery of cytokines secreted from the skeletal muscle (SKM), termed "myokines," has garnered attention due to their positive effects on metabolic processes. Interleukin-15 (IL-15) is a myokine that has numerous positive metabolic effects and is linked to the PPAR family of mitochondrial regulators. Here, we aimed to determine the importance of PPARα and/or PPARδ as targets of IL-15 signaling...
2016: PPAR Research
Heleen H Van Acker, Sébastien Anguille, Yannick Willemen, Johan M Van den Bergh, Zwi N Berneman, Eva Lion, Evelien L Smits, Viggo F Van Tendeloo
BACKGROUND: Adoptive immunotherapy is gaining momentum to fight malignancies, whereby γδ T cells have received recent attention as an alternative cell source as to natural killer cells and αβ T cells. The advent of γδ T cells is largely due to their ability to recognize and target tumor cells using both innate characteristic and T cell receptor (TCR)-mediated mechanisms, their capacity to enhance the generation of antigen-specific T cell responses, and their potential to be used in an autologous or allogeneic setting...
September 29, 2016: Journal of Hematology & Oncology
Gregory Lacraz, Volatiana Rakotoarivelo, Sebastien M Labbé, Mathieu Vernier, Christophe Noll, Marian Mayhue, Jana Stankova, Adel Schwertani, Guillaume Grenier, André Carpentier, Denis Richard, Gerardo Ferbeyre, Julie Fradette, Marek Rola-Pleszczynski, Alfredo Menendez, Marie-France Langlois, Subburaj Ilangumaran, Sheela Ramanathan
OBJECTIVE: IL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues. METHODS: Control and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet...
2016: PloS One
Siwei Shi, Huanhuan Chen, Hua Jiang, Yueqing Xie, Lei Zhang, Ninghuan Li, Chencen Zhu, Junsheng Chen, Han Luo, Jiaxian Wang, Lei Feng, Huili Lu, Jianwei Zhu
Soluble expression of recombinant therapeutic proteins in Escherichia coli (E. coli) has been a challenging task in biopharmaceutical development. In this study, a novel self-cleavable tag Zbasic-intein has been constructed for the soluble expression and purification of a recombinant cytokine, human interleukin-15 (IL-15). We screened several solubilizing tags fused with the self-cleavable Mycobacterium tuberculosis recA mini-intein ∆I-CM and demonstrated that Zbasic tag can significantly improve the solubility of the product with correspondent to the intein activity...
September 28, 2016: Applied Microbiology and Biotechnology
J M Oliver, S C Jenke, J D Mata, A Kreutzer, M T Jones
This study compared the acute cytokine response, and kinetic and kinematic profile following back squat exercise in resistance-trained men. In a randomized, cross-over design, 10 resistance-trained men (27±4 y, 1.80±0.07 m, 82.8±6.7 kg, 16.3±3.5% fat) performed the back squat exercise using traditional and cluster set configurations. Kinetic and kinematic data were sampled throughout each condition. Venous blood was sampled prior, immediately post, 30 min, 60 min, 24 h, and 48 h post-exercise for plasma interleukin-6 (IL-6) and interleukin-15 (IL-15)...
September 27, 2016: International Journal of Sports Medicine
Yunier Rodríguez-Álvarez, Yanelys Morera-Díaz, Haydee Gerónimo-Pérez, Jorge Castro-Velazco, Rafael Martínez-Castillo, Pedro Puente-Pérez, Vladimir Besada-Pérez, Eugenio Hardy-Rando, Araceli Chico-Capote, Klaudia Martínez-Cordovez, Alicia Santos-Savio
BACKGROUND: Interleukin-15 is an immunostimulatory cytokine overexpressed in several autoimmune and inflammatory diseases such as Rheumatoid Arthritis, psoriasis and ulcerative colitis; thus, inhibition of IL-15-induced signaling could be clinically beneficial in these disorders. Our approach to neutralize IL-15 consisted in active immunization with structurally modified human IL-15 (mhIL-15) with the aim to induce neutralizing antibodies against native IL-15. In the present study, we characterized the antibody response in Macaca fascicularis, non-human primates that were immunized with a vaccine candidate containing mhIL-15 in Aluminum hydroxide (Alum), Montanide and Incomplete Freund's Adjuvant...
September 26, 2016: BMC Immunology
Marlies Meisel, Toufic Mayassi, Hannah Fehlner-Peach, Jason C Koval, Sarah L O'Brien, Reinhard Hinterleitner, Kathryn Lesko, Sangman Kim, Romain Bouziat, Li Chen, Christopher R Weber, Sarkis K Mazmanian, Bana Jabri, Dionysios A Antonopoulos
Dysbiosis resulting in gut-microbiome alterations with reduced butyrate production are thought to disrupt intestinal immune homeostasis and promote complex immune disorders. However, whether and how dysbiosis develops before the onset of overt pathology remains poorly defined. Interleukin-15 (IL-15) is upregulated in distressed tissue and its overexpression is thought to predispose susceptible individuals to and have a role in the pathogenesis of celiac disease and inflammatory bowel disease (IBD). Although the immunological roles of IL-15 have been largely studied, its potential impact on the microbiota remains unexplored...
September 20, 2016: ISME Journal
Paolo Zamboni, Paolo Spath, Veronica Tisato, Mirko Tessari, Patrizia Dalla Caneva, Erica Menegatti, Savino Occhionorelli, Sergio Gianesini, Paola Secchiero
BACKGROUND: To assess if suppression of the oscillatory component of reflux may improve the inflammatory phenotype in chronic venous disease (CVD). MATERIALS AND METHODS: From 193 CVD patients, we selected 54 (13 males, 41 females, CEAP C2-4EpAsPr) for a blinded, case-control prospective investigation. All of them underwent echo-color-Doppler assessment of reflux parameters. In the same patients a blood systemic assessment of 19 inflammatory cytokines was obtained...
September 2016: Journal of Surgical Research
Paola Iudicone, Daniela Fioravanti, Elisabetta Cicchetti, Ilaria Grazia Zizzari, Annino Pandolfi, Rita Scocchera, Raffaella Fazzina, Luca Pierelli
CIK cells are a subset of effector lymphocytes endowed with a non-MHC restricted anti-tumor activity making them an appealing and promising cell population for adoptive immunotherapy. CIK are usually generated ex-vivo by initial priming with Interferon-γ (IFN-γ) and monoclonal antibody against CD3 (anti-CD3), followed by culture in medium containing Interleukin-2 (IL-2). Interleukin-15 (IL-15) shares with IL-2 similar biological functions and recently it has been reported to induce CIK with increased anti-leukemic potential...
September 8, 2016: Human Immunology
Julien Ettersperger, Nicolas Montcuquet, Georgia Malamut, Nicolas Guegan, Silvia Lopez-Lastra, Ségolène Gayraud, Christian Reimann, Elodie Vidal, Nicolas Cagnard, Patrick Villarese, Isabelle Andre-Schmutz, Rita Gomes Domingues, Cristina Godinho-Silva, Henrique Veiga-Fernandes, Ludovic Lhermitte, Vahid Asnafi, Elizabeth Macintyre, Christophe Cellier, Kheira Beldjord, James P Di Santo, Nadine Cerf-Bensussan, Bertrand Meresse
The nature of gut intraepithelial lymphocytes (IELs) lacking antigen receptors remains controversial. Herein we showed that, in humans and in mice, innate intestinal IELs expressing intracellular CD3 (iCD3(+)) differentiate along an Id2 transcription factor (TF)-independent pathway in response to TF NOTCH1, interleukin-15 (IL-15), and Granzyme B signals. In NOTCH1-activated human hematopoietic precursors, IL-15 induced Granzyme B, which cleaved NOTCH1 into a peptide lacking transcriptional activity. As a result, NOTCH1 target genes indispensable for T cell differentiation were silenced and precursors were reprogrammed into innate cells with T cell marks including intracellular CD3 and T cell rearrangements...
September 20, 2016: Immunity
Iichiro Okabe, Takeshi Kikuchi, Makio Mogi, Hiroaki Takeda, Makoto Aino, Yosuke Kamiya, Takeki Fujimura, Hisashi Goto, Kousuke Okada, Yoshiaki Hasegawa, Toshihide Noguchi, Akio Mitani
Interleukin-15 (IL-15), a cytokine secreted by several cell types, has important physiological roles in the activity, proliferation, and viability of immune cells.It has both chemoattractant and proinflammatory properties, and may promote bone destruction. Aprevious study has shown that IL-15alone exertsno effect on osteoclastogenesis. Therefore,thecurrent study addressed the synergistic effect of IL-15 on osteoclast formation using RAW264.7(RAW) cellsby co-stimulation with receptor activator of nuclear factor (NF)-κB ligand (RANKL)that has a majorrole inosteoclastogenesis involving the pathogenesis of rheumatoid arthritis and periodontal disease...
September 8, 2016: Journal of Cellular Biochemistry
Margherita Sisto, Loredana Lorusso, Sabrina Lisi
IL-15 is a key regulatory cytokine that shares many biological properties with IL-2. Recently, it has been shown that IL-15 could be up-regulated in T cell-mediated inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel diseases. However, the role and expression of IL-15 in the inflammatory autoimmune disease Sjögren's syndrome (SS) has not been investigated. In the present study we evaluated the expression of IL-15 mRNA and protein in minor salivary gland (MSG) biopsy specimens and in human salivary gland epithelial cell (SGEC) cultures obtained from patients with primary SS (pSS) and compared their expression with that seen in normal healthy control subjects...
October 2016: Pathology
Tsuyoshi Kiniwa, Yutaka Enomoto, Natsumi Terazawa, Ai Omi, Naoko Miyata, Kenji Ishiwata, Atsushi Miyajima
Natural killer (NK) cells are known to be activated by Th1-type cytokines, such as IL-2, -12, or -18, and they secrete a large amount of IFN-γ that accelerates Th1-type responses. However, the roles of NK cells in Th2-type responses have remained unclear. Because IL-4 acts as an initiator of Th2-type responses, we examined the characteristics of NK cells in mice overexpressing IL-4. In this study, we report that IL-4 overexpression induces distinctive characteristics of NK cells (B220(high)/CD11b(low)/IL-18Rα(low)), which are different from mature conventional NK (cNK) cells (B220(low)/CD11b(high)/IL-18Rα(high))...
September 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
Dionysios C Watson, Defne Bayik, Avinash Srivatsan, Cristina Bergamaschi, Antonio Valentin, Gang Niu, Jenifer Bear, Mitchell Monninger, Mei Sun, Aizea Morales-Kastresana, Jennifer C Jones, Barbara K Felber, Xiaoyuan Chen, Ihsan Gursel, George N Pavlakis
Extracellular vesicles (EV), including exosomes and microvesicles, are nano-sized intercellular communication vehicles that participate in a multitude of physiological processes. Due to their biological properties, they are also promising candidates for the systemic delivery of therapeutic compounds, such as cytokines, chemotherapeutic drugs, siRNAs and viral vectors. However, low EV production yield and rapid clearance of administered EV by liver macrophages limit their potential use as therapeutic vehicles...
October 2016: Biomaterials
A M Jones, J L Griffiths, A J Sanders, S Owen, F Ruge, K G Harding, W G Jiang
Chronic wounds represent a significant burden to health services and are associated with patient morbidity. Novel methods to diagnose and/or treat problematic wounds are needed. Interleukin (IL)-15 is a cytokine involved in a number of biological processes and disease states such as inflammation, healing and cancer progression. The current study explores the expression profile of IL-15 and IL-15 receptor α (IL-15Rα) in chronic wounds and its impact on keratinocytes. IL-15 and IL-15Rα expression were examined in healing and non-healing chronic wounds using qPCR and immunohistochemical analysis...
September 2016: International Journal of Molecular Medicine
Xiao Liang, Min Luo, Xia-Wei Wei, Cui-Cui Ma, Yu-Han Yang, Bin Shao, Yan-Tong Liu, Ting Liu, Jun Ren, Li Liu, Zhi-Yao He, Yu-Quan Wei
Interleukin-15 has been implicated as a promising cytokine for cancer immunotherapy, while folate receptor α (FRα) has been shown to be a potentially useful target for colon cancer therapy. Herein, we developed F-PLP/pIL15, a FRα-targeted lipoplex loading recombinant interleukin-15 plasmid (pIL15) and studied its antitumor effects in vivo using a CT26 colon cancer mouse model. Compared with control (normal saline) treatment, F-PLP/pIL15 significantly suppressed tumor growth in regard to tumor weight (P < 0...
July 11, 2016: Oncotarget
Claudia Cappel, Sabine Huenecke, Anica Suemmerer, Stephanie Erben, Eva Rettinger, Verena Pfirrmann, Annekathrin Heinze, Olga Zimmermann, Thomas Klingebiel, Evelyn Ullrich, Peter Bader, Melanie Bremm
BACKGROUND: Neuroblastoma (NB) is the most common solid extracranial tumor in childhood. Despite advances in therapy, the prognosis is poor and optimized therapies are urgently needed. Therefore, we investigated the antitumor potential of interleukin-15 (IL-15)-activated cytokine-induced killer (CIK) cells against different NB cell lines. PROCEDURE: CIK cells were generated from peripheral blood mononuclear cells by the stimulation with interferon-γ (IFN-γ), IL-2, OKT-3 and IL-15 over a period of 10-12 days...
July 19, 2016: Pediatric Blood & Cancer
Anjali Mishra, Krista La Perle, Sonya Kwiatkowski, Laura A Sullivan, Gregory H Sams, Jessica Johns, Douglas P Curphey, Jing Wen, Kathleen McConnell, Jun Qi, Henry Wong, Giandomenico Russo, Jianying Zhang, Guido Marcucci, James E Bradner, Pierluigi Porcu, Michael A Caligiuri
UNLABELLED: Cutaneous T-cell lymphoma (CTCL) is the most common type of primary cutaneous lymphoma. Here, we report that patients with CTCL show increased IL15 in a clinical stage-dependent manner. Mechanistically, we show that ZEB1 is a transcriptional repressor of IL15 in T cells and that hypermethylation of the ZEB1 binding region within the IL15 promoter, as seen in patients with CTCL, prevents ZEB1 binding and causes increased transcription of IL15 Using a transgenic mouse model of IL15, we provide evidence that overexpression of IL15 induces a spontaneous CTCL that mimics the human neoplasm...
September 2016: Cancer Discovery
W Eik, S S Marcon, T Krupek, I T S Previdelli, O C N Pereira, M A R C P Silva, R B Bazotte
We evaluated the impact of postprandial glycemia on blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in non-diabetic patients with symptoms suggesting reactive hypoglycemia. Eleven patients with clinical symptoms suggesting reactive hypoglycemia received an oral glucose solution (75 g) Blood was collected at 0 (baseline), 30, 60, 120 and 180 min after glucose ingestion and the plasma concentrations of interferon-α (IFN-α), interferon-γ (IFN-γ), interleukin-1 receptor antagonist (IL-1RA), interleukin 2 (IL-2), interleukin-2 receptor (IL-2R), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin-12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), IFN-γ inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein-1α (MIP-1α), interleukin-1β (IL-1β), colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), basic fibroblast growth factor (FGF-basic), eotaxin, tumor necrosis factor α (TNFα), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), macrophage inflammatory protein-1α (MIP-1α), and 1β (MIP-1β) were evaluated...
July 11, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Wei Wang, Amy K Erbe, Kory A Alderson, Emily Phillips, Mikayla Gallenberger, Jacek Gan, Dario Campana, Jacquelyn A Hank, Paul M Sondel
Infusion of allogeneic NK cells is a potential immunotherapy for both hematopoietic malignancies and solid tumors. Interactions between killer immunoglobulin-like receptors (KIR) on human NK cells and KIR-ligands on tumor cells influence the magnitude of NK function. To obtain sufficient numbers of activated NK cells for infusion, one potent method uses cells from the K562 human erythroleukemia line that have been transfected to express activating 41BB ligand (41BBL) and membrane-bound interleukin 15 (mbIL15)...
September 2016: Cancer Immunology, Immunotherapy: CII
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