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https://www.readbyqxmd.com/read/29229565/gm-csf-producing-autoreactive-cd4-t-cells-in-type-1-diabetes
#1
Jan Knoop, Anita Gavrisan, Denise Kuehn, Julia Reinhardt, Melanie Heinrich, Markus Hippich, Anne Eugster, Christian Ockert, Anette-Gabriele Ziegler, Ezio Bonifacio
The phenotype of autoreactive T cells in type 1 diabetes is described as Th1, Th17 and/or Th21, but is largely uncharacterized. We combined multi-parameter cytokine profiling and proliferation, and identified GM-CSF producing cells as a component of the response to beta cell autoantigens proinsulin and GAD65. Overall cytokine profiles of CD4+ T cell were not altered in type 1 diabetes. In contrast, patients with recent onset type 1 diabetes had increased frequencies of proinsulin-responsive CD4+CD45RA- T cells producing GM-CSF (p=0...
December 8, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29228979/contrasting-effect-of-the-latency-reversing-agents-bryostatin-1-and-jq1-on-astrocyte-mediated-neuroinflammation-and-brain-neutrophil-invasion
#2
Alizé Proust, Corinne Barat, Mathieu Leboeuf, Jean Drouin, Michel J Tremblay
BACKGROUND: Despite effectiveness of the combined antiretroviral therapy, HIV-1 persists in long-lived latently infected cells. Consequently, new therapeutic approaches aimed at eliminating this latent reservoir are currently being developed. A "shock and kill" strategy using latency-reversing agents (LRA) to reactivate HIV-1 has been proposed. However, the impact of LRA on the central nervous system (CNS) remains elusive. METHODS: We used human fetal astrocytes and investigated the effects of several LRA on their functional and secretory activities...
December 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29225343/advances-in-the-understanding-and-treatment-of-sepsis-induced-immunosuppression
#3
REVIEW
Fabienne Venet, Guillaume Monneret
Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis can induce acute kidney injury and multiple organ failures and represents the most common cause of death in the intensive care unit. Sepsis initiates a complex immune response that varies over time, with the concomitant occurrence of both pro-inflammatory and anti-inflammatory mechanisms. As a result, most patients with sepsis rapidly display signs of profound immunosuppression, which is associated with deleterious consequences...
December 11, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29224368/immune-response-proteins-as-predictive-biomarkers-of-doxorubicin-induced-cardiotoxicity-in-breast-cancer-patients
#4
Li-Rong Yu, Zhijun Cao, Issam Makhoul, Jaclyn R Daniels, Suzanne Klimberg, Jeanne Y Wei, Jane Pf Bai, Jinong Li, Julia T Lathrop, Richard D Beger, Valentina K Todorova
Cancer treatment with doxorubicin (DOX) can induce cumulative dose-dependent cardiotoxicity. Currently, there are no specific biomarkers that can identify patients at risk during the initial doses of chemotherapy. The aim of this study was to examine plasma cytokines/chemokines and potential cardiovascular biomarkers for the prediction of DOX-induced cardiotoxicity. Plasma samples were collected before (T0), and after the first (T1) and the second (T2) cycles of DOX-based chemotherapy of 27 breast cancer patients, including five patients who presented with >10% decline of left ventricular ejection fraction (LVEF), five patients with LVEF decline of 5-10%, and 17 patients who maintained normal LVEF at the end of chemotherapy (240 mg/m2 cumulative dose of DOX from four cycles of treatment)...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29222492/interaction-of-rna-binding-protein-hur-and-mir-466i-regulates-gm-csf-expression
#5
Jing Chen, William Adamiak, Ganlei Huang, Ulus Atasoy, Abdolmohamad Rostami, Shiguang Yu
Granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by T helper 17 (Th17) cells plays an essential role in autoimmune diseases. Transcriptional regulation of Th17 cell differentiation has been extensively studied, but post-transcriptional regulation of Th17 cell differentiation has remained less well characterized. The RNA-binding protein HuR functions to promote the stability of target mRNAs via binding the AU-rich elements of the 3' untranslated region (3'UTR) of numerous pro-inflammatory cytokines including IL-4, IL-13, IL-17 and TNF-α...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29221684/ex-vivo-flush-of-the-limb-allograft-reduces-inflammatory-burden-prior-to-transplantation
#6
Kavit R Amin, Alexandra L Ball, Chandanpreet Chhina, Rebecca J Edge, John P Stone, William R Critchley, Jason K Wong, James E Fildes
BACKGROUND: Passenger leucocytes and inflammatory debris transferred from the donor limb to the recipient can induce allorecognition, which activates the host immune response. This is the first study to evaluate whether the transfer of this inflammatory burden can be reduced via post-preservation flush prior to revascularisation, and whether this is influenced by ischaemia. METHODS: Bilateral forelimbs from the same pig were procured and infused with preservation flush and stored on ice...
November 24, 2017: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
https://www.readbyqxmd.com/read/29221128/mycn-amplified-stage-2-3-neuroblastoma-excellent-survival-in-the-era-of-anti-gd2-immunotherapy
#7
Brian H Kushner, Michael P LaQuaglia, Shakeel Modak, Suzanne L Wolden, Ellen M Basu, Stephen S Roberts, Kim Kramer, Karima Yataghene, Irene Y Cheung, Nai-Kong V Cheung
High-risk neuroblastoma (HR-NB) includes MYCN-amplified stage 2/3, but reports covering anti-GD2 immunotherapy, which recently became standard for HR-NB, do not provide details on this subset. We now report on all 20 MYCN-amplified stage 2/3 patients who received induction chemotherapy at our center during the era of consolidation with anti-GD2 antibody 3F8/ granulocyte-macrophage colony-stimulating factor (GM-CSF) (2000-2015). Early in this period, consolidation included autologous stem-cell transplantation (ASCT)...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29216019/familial-association-of-granulocyte-macrophage-colony-stimulating-factor-autoantibodies-in-inflammatory-bowel-disease
#8
Sandra S Wright, Anna Trauernicht, Erin Bonkowski, Courtney A McCall, Elizabeth A Maier, Ramona Bezold, Kathleen Lake, Claudia Chalk, Bruce C Trapnell, Mi-Ok Kim, Subra Kugathasan, Lee A Denson
OBJECTIVES: Elevated Granulocyte-Macrophage Colony Stimulating Factor auto-antibodies (GM-CSF Ab) are associated with increased intestinal permeability and stricturing behavior in Crohn's Disease (CD). We tested for familial association of serum GM-CSF Ab level in CD and Ulcerative Colitis (UC) families. METHODS: Serum GM-CSF Ab concentration was determined in 230 pediatric CD probands and 404 of their unaffected parents and siblings, and 45 UC probands and 71 of their unaffected parents and siblings...
December 5, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29207327/molecular-mechanism-of-lps-induced-tnf-%C3%AE-biosynthesis-in-polarized-human-macrophages
#9
Erik Schilling, Ronald Weiss, Anja Grahnert, Michael Bitar, Ulrich Sack, Sunna Hauschildt
In response to environmental stimuli such as granulocyte-macrophage or macrophage colony stimulating factor (GM-CSF/M-CSF), macrophages (MΦ) can acquire distinct functional phenotypes that control inflammatory processes on the one hand and contribute to a broad spectrum of pathologies on the other. Potential intervention strategies will require an understanding of the signalling processes that are associated with macrophage polarization. In the present study, we show that M-MΦ produce more IFN-β and IL-10 and a lot less TNF-α than do GM-MΦ in response to LPS...
December 2, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29203425/tgf%C3%AE-1-transduction-enhances-immunomodulatory-capacity-of-neural-stem-cells-in-experimental-autoimmune-encephalomyelitis
#10
Chong Xie, Xing Li, Xiajun Zhou, Zezhi Li, Yuan Zhang, Li Zhao, Yong Hao, Guang-Xian Zhang, Yangtai Guan
Bone marrow-derived neural stem cells (BM-NSCs) have therapeutic effect on EAE, an animal model of multiple sclerosis. However, the beneficial effect is suboptimal due to the limited immunomodulatory capacity of these cells. In this study, we engineered BM-NSCs with inducible TGFβ1, a potent immunosuppressive cytokine, to enhance their anti-inflammatory capacity. We found that i.v. injected TGFβ1-BM-NSCs more effectively suppressed clinical severity, inflammation and demyelination of the central nervous system of EAE mice...
December 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29203226/innately-versatile-%C3%AE-%C3%AE-17%C3%A2-t-cells-in-inflammatory-and-autoimmune-diseases
#11
REVIEW
Pedro H Papotto, Annika Reinhardt, Immo Prinz, Bruno Silva-Santos
IL-17-producing γδ (γδ17) T cells form a versatile subset of cells that respond rapidly to innate stimuli and support the pro-inflammatory functions of different myeloid and lymphoid lineages, being particularly critical in the early stages of inflammatory and autoimmune responses. In mice, under homeostatic conditions, these innate-like lymphocytes are pre-programmed in the fetal thymus, through an intricate process involving both T cell receptor-dependent and -independent signals, which allows them to readily produce IL-17 upon stimulation...
December 1, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29202602/clinical-significance-of-serum-anti-gm-csf-autoantibody-levels-in-autoimmune-pulmonary-alveolar-proteinosis
#12
Masaki Nishimura, Etsuro Yamaguchi, Ayumu Takahashi, Nobuhiro Asai, Eisuke Katsuda, Toyohiro Ohta, Yoshinori Ohtsuka, Kenshi Kosaka, Ayako Matsubara, Hiroyuki Tanaka, Norihito Yokoe, Akihito Kubo, Satoshi Konno, Kenji Baba
AIM: Precise clinical significance of antigranulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody levels in autoimmune pulmonary alveolar proteinosis (aPAP) has not been well studied. METHODS: We obtained sera from 50 healthy controls, 46 aPAP patients, 50 with sarcoidosis, 52 with idiopathic interstitial pneumonia and 75 with pneumoconiosis. The clinical course of aPAP patients was assessed by scoring computed tomography images in 19 patients. RESULTS: The cut-off level of anti-GM-CSF IgG for discrimination between aPAP and other diffuse lung diseases was 2...
December 5, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/29193875/dabigatran-inhibits-intravitreal-thrombin-activity
#13
Jeroen Bastiaans, Verena C Mulder, Jan C van Meurs, Marja Smits-Te Nijenhuis, Conny van Holten-Neelen, P Martin van Hagen, Willem A Dik
PURPOSE: Proliferative vitreoretinopathy (PVR) is a vitreoretinal disorder in which retinal pigment epithelial (RPE) cell activation contributes to both formation of fibrotic retinal membranes and inflammation. Vitreous of patients with PVR contains increased thrombin activity which induces profibrotic and proinflammatory programs in RPE cells. Inhibition of intravitreal thrombin activity may thus represent a therapeutic option for PVR. In this study, we examined the capacity of the clinically available direct thrombin inhibitor dabigatran to inhibit thrombin activity in vitreous fluids...
November 30, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/29193199/muc1-and-survivin-based-dna-vaccine-combining-immunoadjuvants-cpg-and-interleukin-2-in-a-bicistronic-expression-plasmid-generates-specific-immune-responses-and-anti-tumor-effects-in-a-murine-colorectal-carcinoma-model
#14
Chenlu Liu, Yu Xie, Bo Sun, Fei Geng, Fangfang Zhang, Qianqian Guo, Hui Wu, Bin Yu, Jiaxin Wu, Xianghui Yu, Wei Kong, Haihong Zhang
DNA vaccination is a promising cancer treatment due to its safety, but poor immunogenicity limits its application. However, immunoadjuvants, heterogeneous prime-boost strategies and combination with conventional treatments can be used to improve the anti-tumor immune effects. A CpG motif and interleukin 2 (IL-2) cytokine are often used as adjuvants. In this study, a DNA vaccine containing a CpG motif was constructed to evaluate its adjuvant effect. The results show that the cytotoxicity of the DNA vaccine was increased 5-fold, and survival life time was prolonged 2-fold by the CpG motif adjuvant...
November 28, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29190674/a-bayesian-view-of-murine-seminal-cytokine-networks
#15
Michelle L Johnson, Tathagata Dasgupta, Nadia Gopichandran, Sarah L Field, Nicolas M Orsi
It has long been established that active agents in seminal fluid are key to initiating and coordinating mating-induced immunomodulation. This is in part governed by the actions of a network of cytokine interactions which, to date, remain largely undefined, and whose interspecific evolutionary conservation is unknown. This study applied Bayesian methods to illustrate the interrelationships between seminal profiles of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 (p70), IL-13, IL-17, eotaxin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-gamma, keratinocyte-derived chemokine (KC), monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1) alpha, MIP-1beta, regulated on activation normal T cell expressed and secreted (RANTES), tumour necrosis factor (TNF)-alpha, leptin, inducible protein (IP)-10 and vascular endothelial growth factor (VEGF) in a rat model...
2017: PloS One
https://www.readbyqxmd.com/read/29189388/cd11c-targeted-delivery-of-dna-to-dendritic-cells-leads-to-cgas-and-sting-dependent-maturation
#16
Marlene F Laursen, Esben Christensen, Laura L T Degn, Kasper Jønsson, Martin R Jakobsen, Ralf Agger, Emil Kofod-Olsen
Immunotherapeutic activation of tumor-specific T cells has proven to be an interesting approach in anticancer treatment. Particularly, anti-CTLA-4 and anti-PD-1/PD-L1 treatment looks promising, and conceivably, even better clinical results might be obtained if such treatment could be combined with boosting the existing tumor-specific T-cell response. One way to achieve this could be by increasing the level of maturation of dendritic cells locally and in the draining lymph nodes. When exposed to cancer cells, dendritic cells may spontaneously mature because of danger-associated molecular patterns derived from the tumor cells...
November 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29187337/prr-signaling-during-in-vitro-macrophage-differentiation-from-progenitors-modulates-their-subsequent-response-to-inflammatory-stimuli
#17
Alba Martínez, Cristina Bono, Javier Megías, Alberto Yáñez, Daniel Gozalbo, M Luisa Gil
Toll-like receptor (TLR) agonists drive hematopoietic stem and progenitor cells (HSPCs) to differentiate along the myeloid lineage in vitro and also in vivo following infection. In this study, we used an in vitro model of HSPC differentiation to investigate the functional consequences (cytokine production) that exposing HSPCs to various pathogen-associated molecular patterns (PAMPs) and Candida albicans cells have on the subsequently derived macrophages. Mouse HSPCs (Lin- cells) were cultured with GM-CSF to induce macrophage differentiation in the presence or absence of the following pattern recognition receptor (PRR) agonists: Pam3CSK4 (TLR2 ligand), LPS (TLR4 ligand), depleted zymosan (which only activates Dectin-1), or inactivated C...
September 1, 2017: European Cytokine Network
https://www.readbyqxmd.com/read/29185463/il-27-but-not-il-35-inhibits-neuroinflammation-through-modulating-gm-csf-expression
#18
Giacomo Casella, Annamaria Finardi, Hélène Descamps, Federico Colombo, Chiara Maiorino, Francesca Ruffini, Marco Patrone, Massimo Degano, Gianvito Martino, Luca Muzio, Burkhard Becher, Roberto Furlan
IL-27 and IL-35 are heterodimeric cytokines, members of the IL-12 family and considered to have immunomodulatory properties. Their role during neuroinflammation had been investigated using mutant mice devoid of either one of their subunits or lacking components of their receptors, yielding conflicting results. We sought to understand the therapeutic potential of IL-27 and IL-35 delivered by gene therapy in neuroinflammation. We constructed lentiviral vectors expressing IL-27 and IL-35 from a single polypeptide chain, and we validated in vitro their biological activity...
November 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29183867/the-epidermal-growth-factor-receptor-inhibitor-ag1478-inhibits-eosinophilic-inflammation-in-upper-airways
#19
Shino Shimizu, Kumiko Takezawa-Yasuoka, Takao Ogawa, Ichiro Tojima, Hideaki Kouzaki, Takeshi Shimizu
Mucus hypersecretion and eosinophil infiltration are important characteristics of eosinophilic inflammation in upper airways, such as allergic rhinitis and chronic rhinosinusitis with nasal polyp. EGFR transactivation induces mucus and inflammatory cytokine secretion from airway epithelial cells. However, the roles of EGFR in eosinophilic inflammation in upper airways are still unknown. The purpose of the study is to elucidate the effects of the EGFR inhibitor AG1478 on eosinophilic airway inflammation. AG1478 significantly inhibited thrombin-induced GM-CSF secretion from nasal epithelial cells and thrombin-induced secretion of eotaxin-1 and RANTES from nasal fibroblasts...
November 25, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29181671/modifying-effect-of-autotransfusion-of-mesenchymal-stromal-cells-on-the-production-of-reactive-oxygen-species-and-cytokines-by-mononuclear-cells-in-patients-with-chronic-heart-failure
#20
V N Petrov, E V Agaeva, O E Popovkina, A G Konoplyannikov, M A Kaplan, L A Lepekhina, E V Sayapina, I V Semenkova
We studied in vivo modifying effect of autotransfusion of human bone marrow mesenchymal stromal cells on ROS generation and production of cytokines (TNFα,TNFβ, IL-1α, IL-10, IFNγ, and GM-CSF) and PGE2 by mononuclear cells of patients (N=21) with chronic heart failure. These parameters were evaluated prior to (control) and after (immediately and on day 14) intravenous administration of stromal cells in doses of 100-200×106. Immediately after autotransfusion, significant increase of in vitro zymosan-induced chemiluminescence of blood mononuclear cells from 10 patients was observed...
November 27, 2017: Bulletin of Experimental Biology and Medicine
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