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Immune agonist

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https://www.readbyqxmd.com/read/29036438/a-selective-sphingosine-1-phosphate-receptor-1-agonist-sew-2871-aggravates-gastric-cancer-by-recruiting-myeloid-derived-suppressor-cells
#1
Yujing Zhou, Feng Guo
The immune status of tumor microenvironment in gastric cancer is poorly understood, which limits the development of novel strategies in this field. Sphingosine-1-phosphate (S1P) acts as an immune modulator, but the role of S1P in gastric cancer is elusive. Here, we aim to investigate S1P receptor 1 (S1P1)-mediated effect of S1P in gastric cancer. We generated a xenograft mouse model and used SEW-2871, a S1P1 specific agonist to activate S1P1 signaling. Tumor-infiltrating lymphocytes (TILs) were isolated and analyzed using flow cytometry...
October 3, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/29034249/misoprostol-inhibits-lipopolysaccharide-induced-pro-inflammatory-cytokine-production-by-equine-leukocytes
#2
Emily Medlin Martin, Kristen M Messenger, Mary Katherine Sheats, Samuel L Jones
Pro-inflammatory cytokines including tumor necrosis factor α (TNFα), IL-1β, IL-6, and IL-8 are potent immune mediators that exacerbate multiple equine diseases such as sepsis and laminitis. Unfortunately, safe and effective cytokine-targeting therapies are lacking in horses; therefore, novel mechanisms of inhibiting cytokine production are critically needed. One potential mechanism for inhibiting cytokine synthesis is elevation of intracellular cyclic AMP (cAMP). In human leukocytes, intracellular cAMP production is induced by activation of E-prostanoid (EP) receptors 2 and 4...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/29033950/glutathione-fine-tunes-the-innate-immune-response-toward-antiviral-pathways-in-a-macrophage-cell-line-independently-of-its-antioxidant-properties
#3
Marina Diotallevi, Paola Checconi, Anna Teresa Palamara, Ignacio Celestino, Lucia Coppo, Arne Holmgren, Kahina Abbas, Fabienne Peyrot, Manuela Mengozzi, Pietro Ghezzi
Glutathione (GSH), a major cellular antioxidant, is considered an inhibitor of the inflammatory response involving reactive oxygen species (ROS). However, evidence is largely based on experiments with exogenously added antioxidants/reducing agents or pro-oxidants. We show that depleting macrophages of 99% of GSH does not exacerbate the inflammatory gene expression profile in the RAW264 macrophage cell line or increase expression of inflammatory cytokines in response to the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS); only two small patterns of LPS-induced genes were sensitive to GSH depletion...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29031697/ubiquitin-modifying-enzymes-and-regulation-of-the-inflammasome
#4
REVIEW
Michael G Kattah, Barbara A Malynn, Averil Ma
Ubiquitin and ubiquitin-modifying enzymes play critical roles in a wide variety of intracellular signaling pathways. Inflammatory signaling cascades downstream of TNF, TLR agonists, antigen receptor cross-linking, and cytokine receptors, all rely on ubiquitination events to direct subsequent immune responses. In the past several years, inflammasome activation and subsequent signal transduction have emerged as an excellent example of how ubiquitin signals control inflammatory responses. Inflammasomes are multiprotein signaling complexes that ultimately lead to caspase activation and release of the interleukin-1 (IL-1) family members, IL-1β and IL-18...
October 12, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29030320/atp-released-from-astrocytes-modulates-action-potential-threshold-and-spontaneous-excitatory-postsynaptic-currents-in-the-neonatal-rat-prefrontal-cortex
#5
Edward Beamer, Gergely Kovács, Beata Sperlágh
Maternal immune activation during pregnancy is a risk factor for neurodevelopmental disorders, such as schizophrenia; however, a full mechanistic understanding has yet to be established. The activity of a transient cell population, the subplate neurons, is critical for the development of cortical inhibition and functional thalamocortical connections. Sensitivity of these cells to factors released during inflammation, therefore, may offer a link between maternal immune activation and the aberrant cortical development underlying some neuropsychiatric disorders...
October 10, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29029594/chemoreceptors-in-the-gut
#6
S Steensels, I Depoortere
The gastrointestinal tract represents the largest interface between the human body and the external environment. It must continuously monitor and discriminate between nutrients that need to be assimilated and harmful substances that need to be expelled. The different cells of the gut epithelium are therefore equipped with a subtle chemosensory system that communicates the sensory information to several effector systems involved in the regulation of appetite, immune responses, and gastrointestinal motility. Disturbances or adaptations in the communication of this sensory information may contribute to the development or maintenance of disease...
October 13, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/29028529/design-synthesis-and-immunological-evaluation-of-novel-amphiphilic-desmuramyl-peptides
#7
Farooq-Ahmad Khan, Marina Ulanova, Bing Bai, Damayanthi Yalamati, Zi-Hua Jiang
Muramyl dipeptide (MDP) - an essential bacterial cell wall component - is recognized by our immune system as pathogen-associated molecular pattern (PAMP) which results in immune responses with adverse toxic effects. In order to harness the beneficial properties from the pro-inflammatory characteristics of the bacterial cell wall motif, MDP was strategically re-designed while conserving the L-D configurations of the dipeptide moiety. The muramic acid was replaced with a hydrophilic arene and lipophilic chain was introduced at peptide end to give the amphiphilic desmuramyl peptides (DMPs)...
September 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29027376/adenosine-a2a-receptor-agonist-ameliorates-eae-and-correlates-with-th1-cytokine-induced-blood-brain-barrier-dysfunction-via-suppression-of-mlck-signaling-pathway
#8
Ying Liu, Marwan Alahiri, Bianca Ulloa, Boxun Xie, Saud A Sadiq
INTRODUCTION: Multiple sclerosis (MS) disease activity is associated with blood-brain barrier (BBB) disruption, which is mediated by inflammatory cytokines released by CD4+ lymphocytes. To assess the effects of adenosine A2A receptors on BBB permeability in vitro and in vivo. METHODS: A2A receptor expression was detected by immunostaining in experimental autoimmune encephalomyelitis (EAE) C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG)35-55 , and human MS brain...
October 12, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29026145/cibinetide-dampens-innate-immune-cell-functions-thus-ameliorating-the-course-of-experimental-colitis
#9
Manfred Nairz, David Haschka, Stefanie Dichtl, Thomas Sonnweber, Andrea Schroll, Malte Aßhoff, John E Mindur, Patrizia L Moser, Dominik Wolf, Filip K Swirski, Igor Theurl, Anthony Cerami, Michael Brines, Günter Weiss
Two distinct forms of the erythropoietin receptor (EPOR) mediate the cellular responses to erythropoietin (EPO) in different tissues. EPOR homodimers signal to promote the maturation of erythroid progenitor cells. In other cell types, including immune cells, EPOR and the ß-common receptor (CD131) form heteromers (the innate repair receptor; IRR), and exert tissue protective effects. We used dextran sulphate sodium (DSS) to induce colitis in C57BL/6 N mice. Once colitis was established, mice were treated with solvent, EPO or the selective IRR agonist cibinetide...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29023416/neuro-coagulopathy-blood-coagulation-factors-in-central-nervous-system-diseases
#10
REVIEW
Ciro De Luca, Assunta Virtuoso, Nicola Maggio, Michele Papa
Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix...
October 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29022064/proinflammatory-switch-from-g%C3%AE-s-to-g%C3%AE-i-signaling-by-glucagon-like-peptide-1-receptor-in-murine-splenic-monocyte-following-burn-injury
#11
Qing-Hong Zhang, Ji-Wei Hao, Guang-Lei Li, Xiao-Jing Ji, Xu-Dong Yao, Ning Dong, Yong-Ming Yao
OBJECTIVE: Glucagon-like peptide-1 (GLP-1)-based therapy via G protein-coupled receptor (GPCR) GLP-1R, to attenuate hyperglycemia in critical care has attracted great attention. However, the exaggerated inflammation by GLP-1R agonist, Exendin-4, in a mouse model of burn injury was quite unexpected. Recent studies found that GPCR might elicit proinflammatory effects by switching from Gαs to Gαi signaling in the immune system. Thus, we aimed to investigate the possible Gαs to Gαi switch in GLP-1R signaling in monocyte following burn injury...
October 11, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29021396/quiescence-promotes-latent-hiv-infection-and-resistance-to-reactivation-from-latency-with-histone-deacetylase-inhibitors
#12
Mark M Painter, Thomas D Zaikos, Kathleen L Collins
Human immunodeficiency virus type-1 (HIV-1) establishes transcriptionally silent latent infections in many cell types, including resting memory T cells and hematopoietic stem and progenitor cells (HSPCs), which allow the virus to persist in infected individuals despite antiretroviral therapy. Developing in vitro models of HIV-1 latency that recapitulate the characteristics of latently-infected cells in vivo is crucial to identifying and developing effective latency-reversing therapies. HSPCs exist in a quiescent state in vivo, and quiescence is correlated with latent infections in T cells...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29021367/disruption-of-trim9-function-abrogates-macrophage-motility-in-vivo
#13
Debra A Tokarz, Amy K Heffelfinger, Dereje D Jima, Jamie Gerlach, Radhika N Shah, Ivan Rodriguez-Nunez, Amanda N Kortum, Ashley A Fletcher, Shila K Nordone, J McHugh Law, Steffen Heber, Jeffrey A Yoder
The vertebrate immune response comprises multiple molecular and cellular components that interface to provide defense against pathogens. Because of the dynamic complexity of the immune system and its interdependent innate and adaptive functionality, an understanding of the whole-organism response to pathogen exposure remains unresolved. Zebrafish larvae provide a unique model for overcoming this obstacle, because larvae are protected against pathogens while lacking a functional adaptive immune system during the first few weeks of life...
October 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29018828/repurposing-lesogaberan-to-promote-human-islet-cell-survival-and-%C3%AE-cell-replication
#14
Jide Tian, Hoa Dang, Angela Hu, Willem Xu, Daniel L Kaufman
The activation of β-cell's A- and B-type gamma-aminobutyric acid receptors (GABAA-Rs and GABAB-Rs) can promote their survival and replication, and the activation of α-cell GABAA-Rs promotes their conversion into β-cells. However, GABA and the most clinically applicable GABA-R ligands may be suboptimal for the long-term treatment of diabetes due to their pharmacological properties or potential side-effects on the central nervous system (CNS). Lesogaberan (AZD3355) is a peripherally restricted high-affinity GABAB-R-specific agonist, originally developed for the treatment of gastroesophageal reflux disease (GERD) that appears to be safe for human use...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29018444/mucosa-associated-lymphoid-tissue-lymphoma-translocation-protein-1-positively-modulates-matrix-metalloproteinase-9-production-in-alveolar-macrophages-upon-toll-like-receptor-7-signaling-and-influenza-virus-infection
#15
Yu-Hsiang Lee, Juin-Hua Huang, Tzu-Hsuan Chang, Hung-Chih Yang, Betty A Wu-Hsieh
Influenza A virus (IAV) infection causes significant morbidity and mortality worldwide. Matrix metalloproteinase-9 (MMP-9) degrades extracellular matrix and is involved in the pathology of influenza. It has been reported that MMP-9 mediates neutrophil migration in IAV infection. Whether alveolar macrophages, the first immune cells that encounter IAV, produce MMP-9, and the mechanism of its regulation have never been investigated. As Toll-like receptor 7 (TLR7) is one of the receptors in innate immune cells that recognize IAV, we used TLR7 agonists and IAV to stimulate alveolar macrophage MH-S cells, primary macrophages, and bone marrow neutrophils...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29018148/suppression-of-cyp1-members-of-the-ahr-response-by-pathogen-associated-molecular-patterns
#16
Adam G Peres, Robert Zamboni, Irah L King, Joaquín Madrenas
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that triggers a broad response, which includes the regulation of proinflammatory cytokine production by monocytes and macrophages. AHR is negatively regulated by a set of genes that it transcriptionally activates, including the AHR repressor (Ahrr) and the cytochrome P450 1 (Cyp1) family, which are critical for preventing exacerbated AHR activity. An imbalance in these regulatory mechanisms has been shown to cause severe defects in lymphoid cells...
October 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29016879/agonist-ox40-immunotherapy-improves-survival-in-glioma-bearing-mice-and-is-complementary-with-vaccination-with-irradiated-gm-csf-expressing-tumor-cells
#17
Nusrat Jahan, Hammad Talat, William T Curry
Background: Glioma immunotherapy is an active area of clinical investigation. Glioma-associated immunosuppression remains an obstacle to efficacious immunotherapy, and combination approaches are likely necessary for durable success. OX40 is a member of the tumor necrosis factor receptor superfamily that is upregulated on activated lymphocytes, ligation of which results in enhanced activity and may be active against cancer. We sought to confirm the efficacy of agonist anti-OX40 immunotherapy against glioma and hypothesized that it is complementary with irradiated whole tumor cell vaccination...
July 7, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28993635/response-of-human-periodontal-ligament-stem-cells-to-ifn-%C3%AE-and-tlr-agonists
#18
Oleh Andrukhov, Johanna Sang-A Hong, Olena Andrukhova, Alice Blufstein, Andreas Moritz, Xiaohui Rausch-Fan
Periodontal ligament stem cells similarly to the mesenchymal stem cells of other tissues possess immunomodulatory properties, which are regulated by different cytokines, particularly by interferon-γ (IFN-γ). In contrast, less information is provided about the effect of toll-like receptors ligand on immunomodulatory properties of these cells. In the present study we investigated the response of human periodontal ligament stem cells (hPDLSCs) in response to simultaneous stimulation with IFN-γ and toll-like receptor (TLR) agonists...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28987878/co-delivery-of-nucleoside-modified-mrna-and-tlr-agonists-for-cancer-immunotherapy-restoring-the-immunogenicity-of-immunosilent-mrna
#19
Rein Verbeke, Ine Lentacker, Laura Wayteck, Karine Breckpot, Mieke Van Bockstal, Benedicte Descamps, Christian Vanhove, Stefaan C De Smedt, Heleen Dewitte
This study reports on the design of mRNA and adjuvant-loaded lipid nanoparticles for therapeutic cancer vaccination. The use of nucleoside-modified mRNA has previously been shown to improve the translational capacity and safety of mRNA-therapeutics, as it prevents the induction of type I interferons (IFNs). However, type I IFNs were identified as the key molecules that trigger the activation of antigen presenting cells, and as such drive T cell immunity. We demonstrate that nucleoside-modified mRNA can be co-delivered with the clinically approved TLR agonist monophosphoryl lipid A (MPLA)...
October 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28987803/long-acting-%C3%AE-2-adrenoreceptor-agonists-suppress-type-1-interferon-expression-in-human-plasmacytoid-dendritic-cells-via-epigenetic-regulation
#20
Chang-Hung Kuo, San-Nan Yang, Yi-Giien Tsai, Chong-Chao Hsieh, Wei-Ting Liao, Li-Chen Chen, Min-Sheng Lee, Hsuan-Fu Kuo, Ching-Hsiung Lin, Chih-Hsing Hung
The combination of inhaled long-acting β2-adrenoreceptor (LABA) and inhaled glucocorticoid (ICS) is a major therapy for asthma. However, the increased risk of infection is still a concern. Plasmacytoid dendritic cells (pDCs) are the predominant cells producing type 1 interferon (IFN) against infection. The effect of LABA/ICS on type 1 IFN expression in human pDCs is unknown. Circulating pDCs were isolated from healthy human subjects and were pretreated with glucocorticoid (GCS), LABA or a cAMP analog, and were stimulated with Toll-like receptor (TLR) agonist CpG (TLR9) or imiquimod (TLR7) in the presence of IL-3...
October 4, 2017: Pulmonary Pharmacology & Therapeutics
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