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Catharina C Gross, Diana Ahmetspahic, Tobias Ruck, Andreas Schulte-Mecklenbeck, Kathrin Schwarte, Silke Jörgens, Stefanie Scheu, Susanne Windhagen, Bettina Graefe, Nico Melzer, Luisa Klotz, Volker Arolt, Heinz Wiendl, Sven G Meuth, Judith Alferink
OBJECTIVE: To characterize changes in myeloid and lymphoid innate immune cells in patients with relapsing-remitting multiple sclerosis (MS) during a 6-month follow-up after alemtuzumab treatment. METHODS: Circulating innate immune cells including myeloid cells and innate lymphoid cells (ILCs) were analyzed before and 6 and 12 months after onset of alemtuzumab treatment. Furthermore, a potential effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-23 production by myeloid cells and natural killer (NK) cell cytolytic activity was determined...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
Elizabeth M Todd, Julie Y Zhou, Taylor P Szasz, Lauren E Deady, June A D'Angelo, Matthew D Cheung, Alfred H J Kim, Sharon Celeste Morley
Alveolar macrophages are lung-resident sentinel cells that develop perinatally and protect against pulmonary infection. Molecular mechanisms controlling alveolar macrophage generation have not been fully defined. Here we show that the actin-bundling protein L-plastin (LPL) is required for the perinatal development of alveolar macrophages. Mice expressing a conditional allele of LPL (CD11c.Cre(pos)-LPL(fl/fl)) exhibited significant reductions in alveolar macrophages and failed to effectively clear pulmonary pneumococcal infection, showing that immunodeficiency results from reduced alveolar macrophage numbers...
October 6, 2016: Blood
Imran Rashid, Nathalie Moiré, Bruno Héraut, Isabelle Dimier-Poisson, Marie-Noëlle Mévélec
Infection with the parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. No vaccine is currently available, so the design of efficient vaccine strategies is still a topical question. In this study, we evaluated the immunoprophylactic potential of a T. gondii virulence factor, the rhoptry kinase ROP18, in a mouse model of chronic toxoplasmosis: first using a recombinant protein produced in Schneider insect cells adjuvanted with poly I:C emulsified in Montanide SV71 by a parenteral route or adjuvanted with cholera toxin by the nasal route and second using a DNA plasmid encoding ROP18 adjuvanted with GM-CSF ± IL-12 DNA...
October 18, 2016: Medical Microbiology and Immunology
Gabriela Barcenas-Morales, Peter Jandus, Rainer Döffinger
PURPOSE OF REVIEW: Concise overview of the field of anticytokine autoantibodies with a focus on recent developments. RECENT FINDINGS: Advances in particular in the analysis of autoantibodies to IFNγ, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-1 are presented. The target epitope for anti-IFNγ autoantibodies has been found to have high homology to a protein from Aspergillus suggesting molecular mimicry as a mechanism of breaking self-tolerance...
October 13, 2016: Current Opinion in Allergy and Clinical Immunology
Whitney A Greene, Teresa A Burke, Elaine D Por, Ramesh R Kaini, Heuy-Ching Wang
Purpose: The purpose of this study was to characterize the secretion profile of induced pluripotent stem cell-derived retinal pigment epithelium (iPS-RPE) during wound healing. iPS-RPE was used to develop an in vitro wound healing model. We hypothesized that iPS-RPE secretes cytokines and growth factors which act in an autocrine manner to promote migration and proliferation of cells during wound healing. Methods: iPS-RPE was grown in transwells until fully confluent and pigmented...
August 1, 2016: Investigative Ophthalmology & Visual Science
Aleksandar Peric, Cveta Spadijer-Mirkovic, Svjetlana Matkovic-Jozin, Ljiljana Jovancevic, Danilo Vojvodic
Introduction Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a strong proinflammatory cytokine that takes part in allergic nasal inflammation as an eosinophil colony-stimulating factor. However, the role of GM-CSF in non-allergic rhinitis has not been fully explored. Objectives The aim of this investigation was to assess the concentration of GM-CSF in nasal secretions of patients with non-allergic rhinitis with eosinophilia syndrome (NARES) in comparison to patients with perennial allergic rhinitis (PAR) and healthy subjects, as well as to assess the relationship with the degree of eosinophilic inflammation and clinical characteristics of the patients...
October 2016: International Archives of Otorhinolaryngology
A Jézéquel, M Kerjouan, M Lederlin, C Lainé-Caroff, C Camus, P Delaval, S Jouneau
INTRODUCTION: Auto-immune pulmonary alveolar proteinosis is a rare disorder characterized by the accumulation of surfactant proteins in the alveoli. CASE REPORT: We report a case of a 41-year-old smoker, presenting initially with acute respiratory failure. Whole lung lavages were effective initially but only for a few weeks. GM-CSF subcutaneous injections were not effective, and then plasmapheresis were tried. CONCLUSION: This is the fifth report of the use of this treatment in auto-immune pulmonary alveolar proteinosis...
October 13, 2016: Revue des Maladies Respiratoires
Konstantinos A Economou, Dimitra Christopikou, Erika Tsorva, Stephen Davies, Minas Mastrominas, Haris Cazlaris, Michael Koutsilieris, Panagoula Angelogianni, Dimitris Loutradis
PURPOSE: Artificial oocyte activation using calcium ionophores and enhancement of embryonic developmental potential by the granulocyte-macrophage colony-stimulating factor (GM-CSF) have already been reported. In this study, we evaluated the synergistic effect of these two methods on aged human unfertilized oocytes after intracytoplasmic sperm injection (ICSI). Then, we cultured the resulting embryos to the blastocyst stage and screened them for chromosomal abnormalities, to assess the safety of this protocol...
October 14, 2016: Journal of Assisted Reproduction and Genetics
Yi Rang Na, Gyo Jung Gu, Daun Jung, Young Won Kim, Juri Na, Jin Sun Woo, Joo Youn Cho, Hyewon Youn, Seung Hyeok Seok
GM-CSF induces proinflammatory macrophages, but the underlying mechanisms have not been studied thus far. In this study, we investigated the mechanisms of how GM-CSF induces inflammatory macrophages. First, we observed that GM-CSF increased the extent of LPS-induced acute glycolysis in murine bone marrow-derived macrophages. This directly correlates with an inflammatory phenotype because glycolysis inhibition by 2-deoxyglucose abolished GM-CSF-mediated increase of TNF-α, IL-1β, IL-6, and IL-12p70 synthesis upon LPS stimulation...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Konrad Pazdrak, Christof Straub, Rosario Maroto, Susan Stafford, Wendy I White, William J Calhoun, Alexander Kurosky
The mechanisms contributing to persistent eosinophil activation and poor eosinopenic response to glucocorticoids in severe asthma are poorly defined. We examined the effect of cytokines typically overexpressed in the asthmatic airways on glucocorticoid signaling in in vitro activated eosinophils. An annexin V assay used to measure eosinophil apoptosis showed that cytokine combinations of IL-2 plus IL-4 as well as TNF-α plus IFN-γ, or IL-3, GM-CSF, and IL-5 alone significantly diminished the proapoptotic response to dexamethasone...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Caroline Stienne, Michaël F Michieletto, Mehdi Benamar, Nadège Carrié, Isabelle Bernard, Xuan-Hung Nguyen, Yannick Lippi, Fanny Duguet, Roland S Liblau, Stephen M Hedrick, Abdelhadi Saoudi, Anne S Dejean
The transcription factor Foxo3 plays a crucial role in myeloid cell function but its role in lymphoid cells remains poorly defined. Here, we have shown that Foxo3 expression was increased after T cell receptor engagement and played a specific role in the polarization of CD4(+) T cells toward pathogenic T helper 1 (Th1) cells producing interferon-γ (IFN-γ) and granulocyte monocyte colony stimulating factor (GM-CSF). Consequently, Foxo3-deficient mice exhibited reduced susceptibility to experimental autoimmune encephalomyelitis...
October 1, 2016: Immunity
Simone Wicki, Ursina Gurzeler, W Wei-Lynn Wong, Philipp J Jost, Daniel Bachmann, Thomas Kaufmann
Neutrophils are essential players in the first-line defense against invading bacteria and fungi. Besides its antiapoptotic role, the inhibitor of apoptosis protein (IAP) family member X-linked IAP (XIAP) has been shown to regulate innate immune signaling. Whereas the role of XIAP in innate signaling pathways is derived mostly from work in macrophages and dendritic cells, it is not known if and how XIAP contributes to these pathways in neutrophils. Here we show that in response to bacterial lipopolysaccharides (LPS), mouse neutrophils secreted considerable amounts of tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) and, in accordance with earlier reports, XIAP prevented LPS-induced hypersecretion of IL-1β also in neutrophils...
October 13, 2016: Cell Death & Disease
Mahalakshmi Ramadass, Jennifer Linda Johnson, Sergio D Catz
Neutrophil secretory proteins are mediators of systemic inflammation in infection, trauma, and cancer. In response to specific inflammatory mediators, neutrophil granules are mobilized and cargo proteins released to modulate the microenvironment of inflammatory sites and tumors. In particular, GM-CSF, a cytokine secreted by several immune, nonimmune, and tumor cells, regulates neutrophil priming and exocytosis. Whereas a comprehensive understanding of this process is necessary to design appropriate anti-inflammatory therapies, the molecular effectors regulating GM-CSF-dependent priming of neutrophil exocytosis are currently unknown...
October 12, 2016: Journal of Leukocyte Biology
Filippo Ingoglia, Rossana Visigalli, Bianca Maria Rotoli, Amelia Barilli, Benedetta Riccardi, Paola Puccini, Marco Milioli, Maria Di Lascia, Gino Bernuzzi, Valeria Dall'Asta
l-Carnitine, in addition to playing a fundamental role in the β-oxidation of fatty acids, has been recently identified as a modulator of immune function, although the mechanisms that underlie this role remain to be clarified. In this study, we addressed the modulation of l-carnitine transport and expression of related transporters during differentiation of human monocytes to macrophages. Whereas monocytes display a modest uptake of l-carnitine, GM-CSF-induced differentiation massively increased the saturable Na(+)-dependent uptake of l-carnitine...
October 12, 2016: Journal of Leukocyte Biology
A Sheih, W C Parks, S F Ziegler
Airway epithelial cells are among the first to encounter inhaled allergens and can initiate allergic responses by producing pro-Th2 innate cytokines. In this study, we investigated the role of epithelial-derived cytokines in sensitization to a clinically relevant allergen, cockroach allergen (CRA). Among the epithelial-derived cytokines, granulocyte macrophage colony-stimulating factor (GM-CSF) had a central role in the initiation of Th2 allergic responses to CRA. We show that initial exposure to CRA directly activated airway epithelial cells through a TLR4-MyD88-dependent pathway and MyD88 signaling in epithelial cells induced upregulation of GM-CSF during sensitization...
October 12, 2016: Mucosal Immunology
Denise S M Medrado da Costa, Joana Hygino, Thais B Ferreira, Taissa M Kasahara, Priscila O Barros, Clarice Monteiro, Aleida Oliveira, Felipe Tavares, Claudia Cristina Vasconcelos, Regina Alvarenga, Cleonice A M Bento
Vitamin D deficiency is an environmental risk factor for MS, a Th17 cell-mediated autoimmune disease that results in demyelination in the CNS. Therefore, we aimed to evaluate the ability of in vitro 1,25(OH)2D in modulating different Th17 cell subsets in MS patients in remission phase. In the present study, the production of Th17-related cytokines (IL-1β, IL-6, IL-17, IL-22), as well as GM-CSF, was significantly higher in cell cultures from MS patients than in healthy subjects (HS). The 1,25(OH)2D reduced all pro-inflammatory cytokines essayed, mainly those released from HS cell cultures...
October 15, 2016: Journal of Neuroimmunology
Manoj Kumar, Sanjeev Bhoi, Sujata Mohanty, Vineet Kumar Kamal, D N Rao, Pravas Mishra, Sagar Galwankar
BACKGROUND: Hemorrhagic shock (HS) is the major leading cause of death after trauma. Up to 50% of early deaths are due to massive hemorrhage. Excessive release of pro-inflammatory cytokine and hypercatecholamine induces hematopoietic progenitor cells (HPCs) apoptosis, leading to multiorgan failure and death. However, still, result remains elusive for hematopoietic stem cells (HSCs) behavior in trauma HS (T/HS). OBJECTIVES: Therefore, our aim was to evaluate the in vitro HSCs behavior with or without recombinant human erythropoietin (rhEPO), recombinant human granulocyte macrophage-colony-stimulating factor (rhGM-CSF), recombinant human interleukin-3 (rhIL-3) alone, and combination with rhEPO + rhGM-CSF + rhIL-3 (EG3) in T/HS patients...
July 2016: International Journal of Critical Illness and Injury Science
Martine Cordeau, Assila Belounis, Martin Lelaidier, Paulo Cordeiro, Hervé Sartelet, Sabine Herblot, Michel Duval
High-risk neuroblastoma (NB) remains a major therapeutic challenge despite the recent advent of disialoganglioside (GD2)-antibody treatment combined with interleukin (IL)-2 and granulocyte monocyte-colony stimulating factor (GM-CSF). Indeed, more than one third of the patients still die from this disease. Here, we developed a novel approach to improve the current anti-GD2 immunotherapy based on NK cell stimulation using toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDCs). We demonstrated that this strategy led to the efficient killing of NB cells...
2016: PloS One
Mario Rodríguez, Saioa Márquez, Juan Vladimir de la Rosa, Sara Alonso, Antonio Castrillo, Mariano Sánchez Crespo, Nieves Fernández
CREB and STAT3 may control inflammation by several mechanisms, one of the best characterized is the induction of the expression of the anti-inflammatory cytokine IL-10. STAT3 also down-regulates the production of pro-inflammatory cytokines induced by ITAM-coupled receptors, a mechanism termed cross-inhibition. Because signaling via ITAM-dependent mechanisms is a hallmark of fungal pattern receptors, STAT3 activation might be involved in the cross-inhibition associated with invasive fungal infections. The fungal surrogate zymosan produced the phosphorylation of Y705-STAT3 and the expression of Ifnb1 and Socs3, but did not induce the IFN-signature cytokines Cxcl9 and Cxcl10 in BM-derived dendritic cells...
October 6, 2016: Immunology
Galina Kochneva, Galina Sivolobova, Anastasiya Tkacheva, Antonina Grazhdantseva, Olga Troitskaya, Anna Nushtaeva, Anastasiya Tkachenko, Elena Kuligina, Vladimir Richter, Olga Koval
Vaccinia virus (VACV) oncolytic therapy has been successful in a number of tumor models. In this study our goal was to generate a double recombinant vaccinia virus (VV-GMCSF-Lact) with enhanced antitumor activity that expresses exogenous proteins: the antitumor protein lactaptin and human granulocyte-macrophage colony-stimulating factor (GM-CSF). Lactaptin has previously been demonstrated to act as a tumor suppressor in mouse hepatoma as well as MDA-MB-231 human adenocarcinoma cells grafted into SCID mice. VV-GMCSF-Lact was engineered from Lister strain (L-IVP) vaccinia virus and has deletions of the viral thymidine kinase and vaccinia growth factor genes...
September 30, 2016: Oncotarget
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