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Avishai Shemesh, Aleksandra Kugel, Naama Steiner, Michal Yezersky, Dan Tirosh, Avishay Edri, Omri Teltsh, Benyamin Rosental, Eyal Sheiner, Eitan Rubin, Kerry S Campbell, Angel Porgador
NKp44 and NKp30 splice variant profiles have been shown to promote diverse cellular functions. Moreover, microenvironment factors such as TGF-β, IL-15 and IL-18 are able to influence both NKp44 and NKp30 splice variant profiles, leading to cytokine-associated profiles. Placenta and cancerous tissues have many similarities; both are immunologically privileged sites and both share immune tolerance mechanisms to support tissue development. Therefore, we studied the profiles of NKp44 and NKp30 splice variants in these states by comparing (i) decidua from pregnancy disorder and healthy gestation and (ii) matched normal and cancer tissue...
September 27, 2016: Oncotarget
Janet Ayello, Jessica Hochberg, Allyson Flower, Yaya Chu, Laxmi V Baxi, William Quish, Carmella van de Ven, Mitchell S Cairo
NK cells play a significant role in reducing relapse in patients with hematological malignancies following allogeneic stem cell transplantation but NK cell number and naturally occurring inhibitory signals limit their capability. IL-15 and 4-1BBL are important modulators of NK expansion and functional activation. With an aim to overcome these limitations, cord blood (CB) mononuclear cells (MNC) were ex-vivo expanded (EvE) for 7 days with genetically modified K562-mbIL15-41BBL (MODK562) or wildtype K562 (WTK562)...
October 17, 2016: Experimental Hematology
Fengna Li, Yinghui Li, Yehui Duan, Chien-An A Hu, Yulong Tang, Yulong Yin
Skeletal muscle and adipose tissue are the two largest organs in the body. Skeletal muscle is an effector organ, and adipose tissue is an organ that stores energy; in addition, they are endocrine organs that secrete cytokines, namely myokines and adipokines, respectively. Myokines consist of myostatin, interleukin (IL)-8, IL-15, irisin, fibroblast growth factor 21, and myonectin; adipokines include leptin, adiponectin, resistin, chemerin, and visfatin. Furthermore, certain cytokines, such as IL-6 and tumor necrosis factor-α, are released by both skeletal muscle and adipose tissue and exhibit a bioactive effect; thus, they are called adipo-myokines...
October 13, 2016: Cytokine & Growth Factor Reviews
Franz Puttur, Marcela Francozo, Gülhas Solmaz, Carlos Bueno, Marc Lindenberg, Melanie Gohmert, Maxine Swallow, Dejene Tufa, Roland Jacobs, Stefan Lienenklaus, Anja A Kühl, Lisa Borkner, Luka Cicin-Sain, Bernard Holzmann, Hermann Wagner, Luciana Berod, Tim Sparwasser
Cytomegalovirus (CMV) is an opportunistic virus severely infecting immunocompromised individuals. In mice, endosomal Toll-like receptor 9 (TLR9) and downstream myeloid differentiation factor 88 (MyD88) are central to activating innate immune responses against mouse CMV (MCMV). In this respect, the cell-specific contribution of these pathways in initiating anti-MCMV immunity remains unclear. Using transgenic mice, we demonstrate that TLR9/MyD88 signaling selectively in CD11c(+) dendritic cells (DCs) strongly enhances MCMV clearance by boosting natural killer (NK) cell CD69 expression and IFN-γ production...
October 18, 2016: Cell Reports
Jing Ni, Oliver Hölsken, Matthias Miller, Quirin Hammer, Merlin Luetke-Eversloh, Chiara Romagnani, Adelheid Cerwenka
Natural killer (NK) cell infusions can induce remissions in subsets of patients with different types of cancer. The optimal strategies for NK cell activation prior to infusion are still under debate. There is recent evidence that NK cells can acquire long-term functional competence by preactivation with the cytokines IL-12/15/18. The mechanisms supporting the maintenance of long-term NK cell antitumor activity are incompletely under-stood. Here, we show that NK cells preactivated in vitro with IL-12/15/18, but not with IL-15 alone, maintained high antitumor activity even 1 mo after transfer into lymphopenic RAG-2(-/-)γc(-/-) mice...
2016: Oncoimmunology
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
Kevin Looi, Niamh M Troy, Luke W Garratt, Thomas Iosifidis, Anthony Bosco, Alysia G Buckley, Kak-Ming Ling, Kelly M Martinovich, Elizabeth Kicic-Starcevich, Nicole C Shaw, Erika N Sutanto, Graeme R Zosky, Paul J Rigby, Alexander N Larcombe, Darryl A Knight, Anthony Kicic, Stephen M Stick
RATIONALE: No studies have assessed the effects of human rhinovirus (HRV) infection on epithelial tight junctions (TJs) and resultant barrier function. AIM OF THE STUDY: To correlate viral infection with TJ disassembly, epithelial barrier integrity, and function. MATERIALS AND METHODS: Human airway epithelial cells were infected with HRV minor serotype 1B (HRV-1B) at various 50% tissue culture infectivity doses (TCID50) over 72 hours. HRV replication was assessed by quantitative-polymerase chain reaction (qPCR) while cell viability and apoptosis were assessed by proliferation and apoptotic assays, respectively...
October 11, 2016: Experimental Lung Research
Mee Sun Yoon, Chanh Tin Pham, Minh-Trang Thi Phan, Dong-Jun Shin, Youn-Young Jang, Min-Ho Park, Sang-Ki Kim, Seokho Kim, Duck Cho
BACKGROUND AIMS: Few studies have examined the migration pattern of natural killer (NK) cells, especially after radiation treatment for cancer. We investigated whether irradiation can modulate the expression of chemokines in cancer cells and the migration of NK cells to irradiated tumor cells. METHODS: The expression of chemokine receptors (CXCR3, CXCR4 and CXCR6) on interleukin-2 (IL-2)/IL-15-activated NK cells was assessed using flow cytometry. Related chemokine ligands (CXCL11, CXCL12 and CXCL16) in human breast cancer cell lines (MCF7, SKBR3 and MDA-MB231) irradiated at various doses were assessed using reverse transcription-polymerase chain reaction (RT-PCR), fluorescence-activated cell sorting (FACS) and enzyme-linked immunosorbent assay (ELISA)...
October 6, 2016: Cytotherapy
Carolina Landolt-Marticorena, Stephenie D Prokopec, Stacey Morrison, Babak Noamani, Dennisse Bonilla, Heather Reich, James Scholey, Carmen Avila-Casado, Paul R Fortin, Paul C Boutros, Joan Wither
BACKGROUND: Management of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Here, we used a proteomics approach to identify potential urinary biomarkers associated with LN. METHODS: Urine was obtained from 60 LN patients with paired renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using Luminex, 128 analytes were quantified and normalized to urinary creatinine levels...
October 4, 2016: Arthritis Research & Therapy
E L Wu, H X Cui
The prevention and treatment of type-2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), which are disorders with high incidence rates, is of primary importance. In this study, we analyzed the effect of 1,25-(OH)2D3 and lipopolysaccharide (LPS) in combination with interleukin (IL)-15 on the inflammatory immune response and expression of vitamin D receptor (VDR) in mononuclear cells of T2DM and DN uremia (DNU) patients. The human acute monocytic leukemia cell line THP-1 was treated with peripheral blood serum isolated from 30 healthy controls and T2DM and DNU patients each, cultured in the presence or absence of 1,25-(OH)2D3, and subsequently treated with LPS and IL-15...
August 29, 2016: Genetics and Molecular Research: GMR
E V Abakushina, Yu V Marizina, A D Kaprin
We describe a method of activation of lymphocytes isolated from the peripheral blood of patients with cutaneous melanoma and cultured in serum-free medium in the presence of IL-2 and IL-15. Viability, proliferative, cytotoxic, and functional activities of lymphocytes are evaluated. The lymphocytes actively proliferated in this nutrient medium and can be activated in vitro. The method for obtaining sufficient amount of activated lymphocytes can be recommended for adoptive cell immunotherapy of cancer patients...
September 2016: Bulletin of Experimental Biology and Medicine
Robert D Hyldahl, Alyssa Evans, Sunku Kwon, Sarah T Ridge, Eric Robinson, J Ty Hopkins, Matthew K Seeley
INTRODUCTION: Regular exercise protects against degenerative joint disorders, yet the mechanisms that underlie these benefits are poorly understood. Chronic, low-grade inflammation is widely implicated in the onset and progression of degenerative joint disease. PURPOSE: To examine the effect of running on knee intra-articular and circulating markers of inflammation and cartilage turnover in healthy men and women. METHODS: Six recreational runners completed a running (30 min) and control (unloaded for 30 min) session in a counterbalanced order...
October 3, 2016: European Journal of Applied Physiology
Geok Choo Sim, Chengwen Liu, Ena Wang, Hui Liu, Caitlin Creasy, Zhimin Dai, Willem W Overwijk, Jason Roszik, Francesco M Marincola, Patrick Hwu, Elizabeth A Grimm, Laszlo G Radvanyi
Clinical responses to high-dose IL-2 therapy are limited due to selective expansion of CD4+CD25+oxp3+ T-regulatory cells (Tregs) especially ICOS+Tregs, rather than NK cells and effector T cells. These ICOS+Tregs are highly suppressive and constitutively express high levels of IL-2Ralpha (CD25) and CD39. Here, we characterized the effect of a mutant form of IL-2 (F42K), which preferentially binds to the lower affinity IL-2Rbetagamma with reduced binding to CD25, on Tregs, effector NK cells, and T-cell subsets...
October 3, 2016: Cancer Immunology Research
Anna Winberg, Olga Nagaeva, Ivan Nagaev, Catarina Lundell, Ignacio Arencibia, Lucia Mincheva-Nilsson, Eva Rönmark, Christina E West
BACKGROUND: There is need for prognostic markers for symptomatic food allergy since current diagnostic methods are insufficient and/or time and labor consuming. OBJECTIVE: To estimate the cytokine mRNA profiles in peripheral blood mononuclear cells (PBMC) before and after a double-blind placebo-controlled food challenge series in schoolchildren with suspected allergy to milk, egg or cod and in healthy controls. Analyses of fecal inflammatory biomarkers before and after the challenge were included...
December 2016: Cytokine
Salvador Iborra, María Martínez-López, Sofía C Khouili, Michel Enamorado, Francisco J Cueto, Ruth Conde-Garrosa, Carlos Del Fresno, David Sancho
Despite the crucial role of tissue-resident memory T (Trm) cells in protective immunity, their priming remains poorly understood. Here, we have shown differential priming requirements for Trm versus circulating memory CD8(+) T cells. In vaccinia cutaneous-infected mice, DNGR-1-mediated crosspresentation was required for optimal Trm cell priming but not for their skin differentiation or for circulating memory T cell generation. DNGR-1(+) dendritic cells (DCs) promoted T-bet transcription-factor induction and retention of CD8(+) T cells in the lymph nodes (LNs)...
September 24, 2016: Immunity
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
Ida Wergeland, Jörg Assmus, Anne Ma Dyrhol-Riise
BACKGROUND: Interferon gamma release assays (IGRAs) do not discriminate between active tuberculosis (TB) and latent TB infection (LTBI), which limit their use in TB endemic areas. Subjects with QuantiFERON-TB (QFT) results around the diagnostic cut-off more likely show inconsistent results on serial testing which makes the interpretation of the assay difficult. We have studied potential biomarkers in patients with various stages of TB infection and with borderline QFT tests compared to those with higher values...
2016: PloS One
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
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