Three experiments were performed to study the effects of immune challenge on the rewarding properties of opiates. Intraperitoneal injection of polyinosinic-polycytidylic acid (Poly I: C, 1 mg/kg) was used to trigger an immune challenge. Conditioned place preference (CPP) in rats trained with alternating subcutaneous injections of morphine (5 mg/kg) and saline was used to assess the rewarding effect of morphine. Poly I: C administered before CPP training had no effects on CPP acquisition. Poly I: C administered during CPP training enhanced CPP acquisition. Poly I: C administered after morphine-induced CPP acquisition retarded CPP extinction. These results show that the immune challenge by Poly I: C augmented morphine CPP in rats depending on the onset time of the challenge. The findings suggest that immune challenge may enhance the rewarding properties of opiates. Behavioural Pharmacology 21: 369-373 (C) 2010 Wolters Kluwer Health , Lippincott Williams & Wilkins. ...
Maternal Immune Activation Leads to Activated Inflammatory Macrophages in Offspring. http://www.ncbi.nlm.nih.gov/pubmed/24566386 Several epidemiological studies have shown an association between infection or inflammation during pregnancy and increased risk of autism in the child. In addition, animal models have illustrated that maternal inflammation during gestation can cause autism-relevant behaviors in the offspring; so called maternal immune activation…
Schizophrenia patients typically exhibit cognitive impairments that directly affect their daily functioning, but are not effectively treated by current antipsychotics. Maternal immune activation (MIA) during pregnancy, which can be triggered by a variety of infectious agents, has been associated with the development of schizophrenia in adult offspring. Epidemiological evidence indicates that elevated maternal levels of the chemokine interleukin- 8 (IL-8) during MIA contribute to the neurodevelopmental alterations underlying the disorder. The present experiments used an animal model of neurodevelopmental disorders to study the effects of MIA and chemokine receptor antagonism on the behavior of rat offspring, with behavioral tests chosen to examine cognitive functions that are typically impaired in human schizophrenia patients. The viral mimetic polyinosinic-polycytidylic acid (polyI:C) (4.0 mg/kg, i.v.) was injected into pregnant Long-Evans (LE) dams on gestational day (GD) 15. Dams were also ...
Studies were undertaken to characterize mechanisms for NK cell cytokine delivery in vivo. Conditions of systemic IFN-beta expression elicited by polyinosinic-polycytidylic acid (poly(I:C)) treatment or IFN-alpha beta production during lymphocytic choriomeningitis virus or murine cytomegalovirus infections resulted in profound splenic histologic changes, with relocalization of nucleated cells from red to white pulp regions. Cell-trafficking experiments, with fluorescently labeled populations, showed that poly(I:C) induced T/B cell-dependent leukocyte migration into white pulp regions. Splenic leukocytes prepared from severe combined immunodeficient (SCID) and bone marrow cells prepared from SCID or normal C57BL/6 mice revealed a unique poly(I:C)-induced accumulation of non-T/non-B cells along splenic red and white pulp region borders characteristic of marginal zones. Lymphocytic choriomeningitis virus and murine cytomegalovirus infections also induced this trafficking pattern. Ab treatments of ...
T cell proliferation in vivo is presumed to reflect a T cell receptor (TCR)-mediated polyclonal response directed to various environmental antigens. However, the massive proliferation of T cells seen in viral infections is suggestive of a bystander reaction driven by cytokines instead of the TCR. In mice, T cell proliferation in viral infections preferentially affected the CD44hi subset of CD8+ cells and was mimicked by injection of polyinosinic-polycytidylic acid [poly(I:C)], an inducer of type I interferon (IFN I), and also by purified IFN I; such proliferation was not associated with up-regulation of CD69 or CD25 expression, which implies that TCR signaling was not involved. IFN I [poly(I:C)]-stimulated CD8+ cells survived for prolonged periods in vivo and displayed the same phenotype as did long-lived antigen-specific CD8+ cells. IFN I also potentiated the clonal expansion and survival of CD8+ cells responding to specific antigen. Production of IFN I may thus play an important role in the ...
Inflammatory skin diseases such as atopic dermatitis and psoriasis represent a complex interaction between the skin and infiltrating immune cells, resulting in damage to the skin barrier and increased inflammation. Polymorphisms in PHF11 have been associated with dermatitis and allergy and PHF11 regulates the transcription of T-cell cytokines as well as class switching to IgE in activated B-cells. The importance of skin barrier homeostasis in the context of inflammatory skin diseases, together with reports identifying PHF11 as an interferon-induced gene, have led us to examine its role in the innate immune response of keratinocytes. We developed a cell culture model that allowed us to analyze the effects of the double-stranded RNA analogue poly(I:C) on a confluent cell monolayer immediately after a 24-h treatment, as well as three days after withdrawal of treatment. Immediately after treatment with poly(I:C), PHF11, IL8, and interferon-dependent ISG15 RNA expression was increased. This was accompanied
Viruses can inadvertently announce their presence by displaying tell-tale patterns-often in the form of their own double-stranded (ds) RNA-and hosts have evolved a panoply of intracellular factors to detect and decode these signals and to set in motion a cascade of antiviral responses. Recently two pattern recognition receptors, RIG-1 and MDA-5, were found to act as RNA helicases and signaling adaptor proteins.. Kato et al. and Gitlin et al. show that RIG-1 and MDA-5 are distinct in their tastes for viral dsRNAs. Thus, mice lacking the MDA5 gene lost the ability to generate a type I interferon response to the dsRNA analog polyinosinic acid: polycytidylic acid [poly(I):poly(C)] and were more susceptible to infection with picornavirus. Kato et al. further compared this MDA5-dependent response with what happened in mice deficient in RIG-1 and found a requirement for RIG-1 in generating immunity to other dsRNA viruses, such as influenza and paramyxoviruses. With further antiviral dsRNA detectors ...
The role of inflammation in the progression of neurodegenerative disease remains unclear. We have shown that systemic bacterial insults accelerate disease progression in animals and in patients with Alzheimers disease. Disease exacerbation is associated with exaggerated CNS inflammatory responses to systemic inflammation mediated by microglia that become primed by the underlying neurodegeneration. The impact of systemic viral insults on existing neurodegenerative disease has not been investigated. Polyinosinic:polycytidylic acid (poly I:C) is a toll-like receptor-3 (TLR3) agonist and induces type I interferons, thus mimicking inflammatory responses to systemic viral infection. In the current study we hypothesized that systemic challenge with poly I:C, during chronic neurodegenerative disease, would amplify CNS inflammation and exacerbate disease. Using the ME7 model of prion disease and systemic challenge with poly I:C (12 mg/kg i.p.) we have shown an amplified expression of IFN-alpha and ...
Inflammatory licensed mesenchymal stem cells (MSCs) have the ability to promote functional tissue repair. This study specifically sought to understand how the recipient tissue environment reciprocally affects MSC function. Inflammatory polarized macrophages, modeling an injured tissue environment, were exposed to licensed MSCs, and the resultant effects of MSC immunomodulation and functionality of the MSC secretome on chondrocyte homeostasis were studied. Inflammatory licensed MSCs were generated through priming with either IFN-γ or polyinosinic:polycytidylic acid (poly I:C). Macrophages were polarized to an inflammatory phenotype using IFN-γ. Licensed MSCs were co-cultured with inflammatory macrophages and immunomodulation of MSCs was assessed in a T-cell proliferation assay. MSC gene expression was analyzed for changes in immunogenicity (MHC-I, MHC-II), immunomodulation (IDO, PTGS2, NOS2, TGF-β1), cytokine (IL-6, IL-8), and chemokine (CCL2, CXCL10) expression. Macrophages were assessed for changes
We have found strong supporting evidence for the helical structures of single-stranded nucleic acids by stretching individual molecules of polyadenylic acid [poly(A)] and polycytidylic acid [poly(C)]. Analyzing the force versus extension data using a two-state elastic model in which random-coil domains alternate with rigid helical domains allows one to extract the thermodynamic and structural properties. In addition, it also yields moderate to low cooperativity of the helix-coil transition for poly(A) and poly(C), respectively. Single stranded (ss) nucleic acids (NA) can form rigid helical domains. These are thought to arise because of stacking interactions favoring parallel orientation of adjacent aromatic rings of the bases leading to weakly cooperative helix-coil transition. The evidence for stacking of NA in solution is mostly based on calorimetric measurements and spectroscopy. The thermodynamic parameters extracted from these measurements are not consistent and vary over a wide range. Furthermore
The initiation of an immune response is dependent on the activation and maturation of dendritic cells after sensing pathogen associated molecular patterns by pattern recognition receptors. However, the response needs to be balanced as excessive pro-inflammatory cytokine production in response to viral or stress-induced pattern recognition receptor signaling has been associated with severe influenza A virus (IAV) infection. Here, we use an inhibitor of Toll-like receptor (TLR)3, a single-stranded oligonucleotide (ssON) with the capacity to inhibit certain endocytic routes, or a TLR3 agonist (synthetic double-stranded RNA PolyI:C), to evaluate modulation of innate responses during H1N1 IAV infection. Since IAV utilizes cellular endocytic machinery for viral entry, we also assessed ssONs capacity to affect IAV infection. We first show that IAV infected human monocyte-derived dendritic cells (MoDC) were unable to up-regulate the co-stimulatory molecules CD80 and CD86 required for T cell activation.
Video articles in JoVE about animal husbandry include A Protocol for Housing Mice in an Enriched Environment, Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C), Zebrafish In Situ Spinal Cord Preparation for Electrophysiological Recordings from Spinal Sensory and Motor Neurons, Rodent Handling and Restraint Techniques, Sampling Strategies and Processing of Biobank Tissue Samples from Porcine Biomedical Models, Using Terminal Transferase-Mediated Dutp Nick End-Labelling (TUNEL) And Caspase 3/7 Assays to Measure Epidermal Cell Death In Frogs With Chytridiomycosis, A Simple Critical-sized Femoral Defect Model in Mice, Construction of an Affordable and Easy-to-Build Zebrafish Facility, Busulfan as a Myelosuppressive Agent for Generating Stable High-level Bone Marrow Chimerism in Mice, Environmental Modulations of the Number of Midbrain Dopamine Neurons in Adult Mice, Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium
In 2010, a large study, which included all children born in Denmark between 1980 and 2005, highlighted an association between women who suffered an infection severe enough to require hospitalization while pregnant, and the presence of autism spectrum disorder (ASD) in their offspring: mothers who experienced a viral infection in the first trimester, or a bacterial infection in the second trimester, were much more likely to have a child with ASD. This phenomenon can be modeled in pregnant mice subjected to immune activation with specific antigens.. Now, results from a study recently (February 26, 2016) published in the journal Science (The maternal interleukin-17a pathway in mice promotes autismlike phenotypes in offspring) reveal a possible mechanism at the basis of the previous observations. The researchers injected pregnant mice with synthetic double-stranded RNA, a mimic of viral infection that induces severe inflammation. They found that the induced inflammatory response in the mother ...
Infections during pregnancy and adolescent cannabis use have both been identified as environmental risk factors for schizophrenia. We combined these factors in an animal model and looked at their effects, alone and in combination, on serotonin 5HT1A receptor binding (5HT1AR) binding longitudinally from late adolescence to adulthood. Pregnant rats were exposed to the viral mimic poly I:C on embryonic day 15. Adolescent offspring received daily injections of the cannabinoid HU210 for 14 days starting on postnatal day (PND) 35. Hippocampal and cortical 5HT1AR binding was quantified autoradiographically using [3H]8-OH-DPAT, in late adolescent (PND 55), young adult (PND 65) and adult (PND 90) rats. Descendants of poly I:C treated rats showed significant increases of 15?18% in 5HT1AR in the hippocampus (CA1) compared to controls at all developmental ages. Offspring of poly I:C treated rats exposed to HU210 during adolescence exhibited even greater elevations in 5HT1AR (with increases of 44, 29, and ...
IL-17 is linked to increased immunopathology in several viral infections (1-3), but the molecular mechanisms behind its role remain largely undefined. In this study, we demonstrate that IL-17 specifically boosts proinflammatory, but not antiviral, gene expression in human cells infected with RSV or stimulated with the viral mimic poly(I:C). Moreover, we investigate the molecular mechanisms behind the synergistic effect of IL-17 and viral signaling, which at the transcriptional level involves IKKs and transcription factors IRF3 and RelA. It would therefore be interesting to assess whether the IKK inhibitors, which we show interfere with IL-17/poly(I:C) synergistic induction of proinflammatory genes in vitro, could be used to block IL-17-dependent responses in vivo.. IL-17 is known to trigger TNF-α-induced cytokine mRNA stabilization (15). However, in our system, poly(I:C)/IL-17 synergy is independent of TNF-α, as TNF protein is not detectable in HSFs infected with RSV or stimulated with ...
Background: Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders such as autism and schizophrenia, as well as seizure development. The amygdala is a brain region involved in the regulation of ...
Pubmed 19729616 Authors: Amit I,Garber M,Chevrier N,Leite AP,Donner Y,Eisenhaure T,Guttman M,Grenier JK,Li W,Zuk O,Schubert LA,Birditt B,Shay T,Goren A,Zhang X,Smith Z,Deering R,McDonald RC,Cabili M,Bernstein BE,Rinn JL,Meissner A,Root DE,Hacohen N,Regev A ...
TRIM25 is involved in MDA5-mediated antiviral signaling. (A) Effect of TRIM25 depletion on polyI:C induced interferon-β synthesis. HEK293T cells were transfect
TY - JOUR. T1 - TLR3 ligand Poly IC Attenuates Reactive Astrogliosis and Improves Recovery of Rats after Focal Cerebral Ischemia. AU - Li, Yang. AU - Xu, Xu Lin. AU - Zhao, Dan. AU - Pan, Lin Na. AU - Huang, Chun Wei. AU - Guo, Lian Jun. AU - Lu, Qing. AU - Wang, Jian. PY - 2015/11/1. Y1 - 2015/11/1. N2 - Aims: Brain ischemia activates astrocytes in a process known as astrogliosis. Although this process has beneficial effects, excessive astrogliosis can impair neuronal recovery. Polyinosinic-polycytidylic acid (Poly IC) has shown neuroprotection against cerebral ischemia-reperfusion injury, but whether it regulates reactive astrogliosis and glial scar formation is not clear. Methods: We exposed cultured astrocytes to oxygen-glucose deprivation/reoxygenation (OGD/R) and used a rat middle cerebral artery occlusion (MCAO)/reperfusion model to investigate the effects of Poly IC. Astrocyte proliferation and proliferation-related molecules were evaluated by immunostaining and Western blotting. ...
Double-stranded (ds) RNA interference (RNAi) is widely used as a reverse genetic approach for functional analysis of plant genes. Constitutive or transient RNAi effects in plants have been achieved vi
Hepatitis C virus (HCV) infection is frequently complicated by glomerulonephritis with immune complexes containing viral RNA. We examined the potential influence of Toll-like receptors (TLRs), specifically TLR3 recognition of viral dsRNA exemplified by polyriboinosinic:polyribocytidylic acid [poly(I:C) RNA]. Normal human kidney stained positive for TLR3 on mesangial cells (MCs), vascular smooth muscle cells, and collecting duct epithelium. Cultured MCs have low TLR3 mRNA levels with predominant intracellular protein localization, which was increased by tumor necrosis factor-alpha, interleukin (IL)-1beta, interferon (IFN)-gamma, and the TLR3 ligand poly(I:C) RNA. Poly(I:C) RNA stimulation of MCs increased mRNA and protein synthesis of IL-6, IL-1beta, M-CSF, IL-8/CXCL8, RANTES/CCL5, MCP-1/CCL2, and ICAM-I; it also increased anti-proliferative and proapoptotic effects, the latter of which was decreased by inhibiting caspase-8. In microdissected glomeruli of normal and non-HCV membranoproliferative ...
In this study we report for the first time expression of Oct-6 in fibroblasts and macrophages. We show that Oct-6 is induced by IFNβ and IFNγ, but not by IL-6. Expression of Oct-6 in response to IFNβ occurs mainly via the canonical Jak/Stat signalling cascade and is dependent on the presence of Stat1 and to a lesser extent on Tyk2. Notably, we observed delayed and low levels of Oct-6 induction in the absence of Stat1 in response to high dose of exogenous IFNβ, suggesting that additional IFN activated factors can mediate Oct-6 induction. Oct-6 is also expressed during viral infection and after treatment with the synthetic dsRNA analogue poly(I:C), in both cases mediated by autocrine/paracrine IFNα/β signalling. Using ChIP technology, we show that Stat1 directly binds to the Oct-6 promoter at around 387 to 481 bp upstream of the transcription start site, a region containing three conserved Stat1 consensus binding sites (i.e. two GAS sites and one imperfect ISRE). The presence of GAS and ISRE ...
BACKGROUND: Excessive iodine intake and viral infection are recognized as both critical factors associated with autoimmune thyroid diseases. Toll-like receptors (TLRs) have been reported to play an important role in autoimmune and inflammatory disorders. In this study, we aimed to clarify the possible mechanism of TLR3 involved in polyinosine-polycytidylic acid (poly(I:C)) promoting excessive iodine intake induced thyroiditis in non-obese diabetic (NOD) mice. METHODS: Both NOD and BALB/c mice were randomly assigned to four groups: control group (n = 5), high iodine intake (HI) group (n = 7), poly(I:C) group (n = 7) and combination of excessive iodine and poly(I:C) injection (HIP) group (n = 7 ...
Unlike typical naive T cells, T cells with an activated (CD44hi) memory phenotype show a rapid rate of proliferation in vivo . The turnover of memory-phenotype CD8+ T cells can be considerably augmented by injecting mice with various compounds, including polyinosinic-polycytidylic acid, lipopolysaccharide and immunostimulatory DNA (CpG DNA). Certain cytokines, notably type I (α, β) interferons (IFNI), have a similar effect. These agents appear to induce proliferation of CD44hi CD8+ cells in vivo by an indirect process involving production of effector cytokines, possibly interleukin-15, by antigen-presenting cells. Although none of the agents tested induces proliferation of naive-phenotype T cells, IFN-I has the capacity to cause upregulation of surface markers on purified naive T cells. Depending upon the experimental conditions used, IFN-I can either inhibit or enhance primary responses of naive T cells to specific antigen.. ...
Viral infections and local production of IFNgamma might contribute to beta-cell dysfunction/death in Type 1 diabetes. Double stranded RNA accumulates in the cytosol of viral-infected cells, and exposure of purified rat beta cells to dsRNA (polyinosinic-polycytidylic acid, PIC) in combination with IFNgamma results in beta-cell dysfunction and apoptosis. To elucidate the molecular mechanisms involved in PIC + IFNgamma-effects, we determined the global profile of genes modified by these agents in primary rat beta cells. FACS-purified rat beta cells were cultured for 6 or 24 h in control condition or with IFNgamma, PIC or a combination of both agents. The gene expression profile was analyzed in duplicate with the Affymetrix RG U34A microarray.
Exosomes can be isolated from easy accessible body fluids, and most importantly, they can at once which is better viagra or cialis provide with several biomarkers, with different levels of specificity. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. Root in-growth bags were used to observe the dynamics of root growth at different soil depths and above-ground growth was also assessed to identify whole-plant growth phenology.. Two-hundred broiler-type chickens were reared under either normal what is cialis lighting or darkness for 16 weeks. Trx 1 overexpression has been shown to be effective in a wide variety of animal models for oxidative and inflammatory disorders. The possibility of underlying neurologic abnormality should be considered in patients with PHPV, particularly those with bilateral disease.. Further, mammary tumor cells of differing metastatic potential were susceptible to polyinosinic-polycytidylic acid activated ...
There is a growing need for novel vaccine adjuvants that can provide safe and potent T-helper type 1 (Th1) activity. RNA-like immune response modifiers (IRMs) are candidate T-cell adjuvants that skew acquired immune responses towards a Th1 phenotype. We set out to delineate the essential signaling pathways by which the RNA-like IRMs, resiquimod (R-848) and polyinosinic:polycytidylic acid (poly I:C), augment CD4+ T-helper 1 (Th1) responses. Highly purified murine conventional dendritic cells (cDCs) and conventional CD4+ T-cells were co-cultured in allogeneic and MHC congenic mixed leukocyte reactions. The activation of CD4+ Th1 cells was examined utilizing cells from mice deficient in specific RNA-sensing pattern recognition receptors and signaling mediators. R-848 and poly I:C stimulation of Type I interferon production and signaling in cDCs was essential but not sufficient for driving CD4+ Th1 responses. The early and rapid production of IL-1alpha and IL-1beta was equally critical for the optimal
The American Society for Microbiology (ASM) is the oldest and largest single life science membership organization in the world. Membership has grown from 59 scientists in 1899 to more than 39,000 members today, with more than one third located outside the United States. The members represent 26 disciplines of microbiological specialization plus a division for microbiology educators.
Researchers at UC Davis have published a study that illustrates how maternal immune activation could affect neurodevelopment in offspring.
Results of the study showed evidence of immune system-mediated subtype of autism that could have diagnostic and treatment implications.. "Our results build on existing research by showing an association between maternal immune activation caused by asthma and allergies and ASD symptom severity in children with ASD," PhD candidate and study author Shrujna Patel from the University of Sydney said. She led the study with her colleagues at the Brain and Mind Centre, Childrens Hospital Westmead, Macquarie University and the Telethon Kids Institute.. Natalie Pollard, an academic from the University of Sydney and mother to Ethan who has autism, thinks that the findings are a positive step toward understanding the intricacies of the disorder and its factors better.. "I knew something wasnt quite right early on, and his development was slower and he would scream for hours," she said. "As a mum, I think the findings are great, because we need more information out there and it could potentially help solve ...
A blog post discussing research suggestive that maternal immune activation and in particular autoantibodies reactive to foetal brain tissue might form a specific subset of autism
The cellular localisation of many innate signalling events following viral infection has yet to be elucidated, however there has been a few cases in which membranes of certain cellular organelles have acted as platforms to these events. Of these, lipid droplets (LDs) have recently been identified as signalling platforms for innate TLR7 and 9 signalling. Despite their wide range of similar roles in various metabolic pathways, LDs have been overlooked as potential platforms for antiviral innate signalling events. This study established an in vitro model to evaluate the efficiency of the early innate immune response in cells with reduced LD content to the viral mimics, dsDNA and dsRNA, and Sendai viral infection. Using RT-qPCR, the expression of IFN- and IFN-λ was quantified following stimulation along with the expression of specific ISGs. Luciferase based assays evaluated the combined expression of ISRE-promoter driven ISGs under IFN- stimulation. Cellular LD content did not alter the entry of ...
The availability of the human genome sequence has revolutionized the strategy of employing nucleic acids with sequences complementary to specific target genes to improve drug discovery and target validation. Development of sequence-specific DNA or RNA analogs that can block the activity of selected single-stranded genetic sequences offers the possibility of rational design with high specificity, lacking in many current drug treatments for various diseases including cancer, at relatively inexpensive costs. Antisense technology is one such example that has shown promising results and boasts of yielding the only approved drug to date in the genomics field. However, in vivo delivery issues have yet to be completely overcome for widespread clinical applications. In contrast to antisense oligonucleotides, the mechanism of silencing an endogenous gene by the introduction of a homologous double-stranded RNA (dsRNA), transgene or virus is called post-transcriptional gene silencing (PTGS) or RNA ...
The Atlantic cod (Gadus morhua) is an important species for global fisheries and aquaculture industries. A thorough knowledge of the genes and molecular pathways involved in Atlantic cod immune responses will likely lead to the development of new diagnostics, vaccines, and other methods of combating infectious diseases that threaten these industries. Using functional genomic approaches, this research investigated the innate immune response in immune tissues (head kidney and spleen) of Atlantic cod following treatment with bacterial antigens (i.e. formalin-killed, atypical Aeromonas salmonicida, referred to as ASAL) or a viral mimic (i.e. polyriboinosinic polyribocytidylic acid, referred to as pIC). This research led to the identification of 4154 expressed sequence tags (ESTs) that were generated from cDNA libraries enriched for transcripts dysregulated following stimulation with ASAL. From these transcripts, 10 genes with immune-relevant functional annotations were selected for quantitative ...
Peptidoglycan recognition proteins (PGRPs) are pattern recognition molecules of innate immunity. In this study, a long-form PGRP, designated as gcPGRP6, was identified from grass carp Ctenopharyngodon idella. The deduced amino acid sequence of gcPGRP6 is composed of 464 residues with a conserved PGRP domain at the C-terminus. The gcPGRP6 gene consists of four exons and three introns, spacing approximately 2.7 kb of genomic sequence. Phylogenetic analysis demonstrated that gcPGRP6 is clustered closely with zebrafish PGLYRP6, and formed a long-type PGRP subfamily together with PGLYRP2 members identified in teleosts and mammals. Real-time PCR and Western blotting analyses revealed that gcPGRP6 is constitutively expressed in organs/tissues examined, and its expression was significantly induced in liver and intestine of grass carp in response to PGN stimulation and in CIK cells treated with lipoteichoic acid (LTA), polyinosinic polycytidylic acid (Poly I:C) and peptidoglycan (PGN). Immunofluorescence ...
TY - JOUR. T1 - Alternaria inhibits double-stranded RNA-induced cytokine production through toll-like receptor 3. AU - Wada, Kota. AU - Kobayashi, Takao. AU - Matsuwaki, Yoshinori. AU - Moriyama, Hiroshi. AU - Kita, Hirohito. PY - 2013/4/12. Y1 - 2013/4/12. N2 - Background: Fungi may be involved in asthma and chronic rhinosinusitis (CRS). Peripheral blood mononuclear cells from CRS patients produce interleukin (IL)-5, IL-13 and interferon (IFN)-γ in the presence of Alternaria. In addition, Alternaria produces potent Th2-like adjuvant effects in the airway. Therefore, we hypothesized that Alternaria may inhibit Th1-type defense mechanisms against virus infection. Methods: Dendritic cells (DCs) were generated from mouse bone marrow. The functional responses were assessed by expression of cell surface molecules by FACS (MHC class II, CD40, CD80, CD86 and OX40L). Production of IL-6, chemokine CXCL10 (IP-10), chemokine CXCL11 (I-TAC) and IFN-β was measured by ELISA. Toll-like receptor 3 (TLR3) mRNA ...
Looking for online definition of Melanoma differentiation-associated protein 6 in the Medical Dictionary? Melanoma differentiation-associated protein 6 explanation free. What is Melanoma differentiation-associated protein 6? Meaning of Melanoma differentiation-associated protein 6 medical term. What does Melanoma differentiation-associated protein 6 mean?
PRIMARY OBJECTIVES:. I. To determine whether the immune response to cancer/testis antigen 1B (NY-ESO-1) elicited by vaccination with CDX-1401 (anti-DEC205-NY-ESO-1 fusion protein vaccine) plus polyinosinic-polycytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose (poly-ICLC) is substantially increased by prior expansion in the number of circulating dendritic cells (DC) by therapy with CDX-301 (fms-related tyrosine kinase 3 ligand [Flt3L]) (recombinant flt3 ligand).. SECONDARY OBJECTIVES:. I. To assess the effect of the vaccine regimen on immune responses to other ongoing and nascent antitumor response antigens associated with melanoma (e.g., preferentially expressed antigen in melanoma [PRAME], melanoma antigen family A, 3 [MAGE-A3], tumor protein p53 [p53], and premelanosome protein [gp100]) as well as memory viral responses (influenza A) and chronic viral responses (cytomegalovirus [CMV], Epstein-Barr virus [EBV]).. II. To assess the effect of the vaccine regimen on the ...
The objectives of this study were to determine the safety and efficacy of polyinosinic-polycytidylic acid stabilized with poly-l-lysine and carboxymethylcellulose (poly-ICLC) when added to radiation and temozolomide (TMZ) in adults with newly diagnosed glioblastoma (GB). Patients received external b …
Biobreeding (BB) rats model type 1 autoimmune diabetes (T1D). BB diabetes-prone (BBDP) rats develop T1D spontaneously. BB diabetes-resistant (BBDR) rats develop T1D after immunological perturbations that include regulatory T cell (Treg) depletion plus administration of low doses of a TLR ligand, polyinosinic-polycytidylic acid. Using both models, we analyzed CD4+CD25+ and CD4+CD45RC- candidate rat Treg populations. In BBDR and control Wistar Furth rats, CD25+ T cells comprised 5-8% of CD4+ T cells. In vitro, rat CD4+CD25+ T cells were hyporesponsive and suppressed T cell proliferation in the absence of TGF-beta and IL-10, suggesting that they are natural Tregs. In contrast, CD4+CD45RC(-) T cells proliferated in vitro in response to mitogen and were not suppressive. Adoptive transfer of purified CD4+CD25+ BBDR T cells to prediabetic BBDP rats prevented diabetes in 80% of recipients. Surprisingly, CD4+CD45RC-CD25- T cells were equally protective. Quantitative studies in an adoptive cotransfer model
Reagents. Natural human CXCL8 and CCL2 were purified to homogeneity from monocyte-derived, conditioned medium (Van Damme et al., 1989, 1997). Recombinant human CXCL12 and human CXCL8(6-77), used in the ERK phosphorylation assay, were obtained from Peprotech (Rocky Hill, NJ). Synthetic CXCL12(1-68) and CXCL12(3-68) and the CC chemokine CCL7 were synthesized by solid-phase peptide synthesis using fluorenylmethoxy-carbonyl (Fmoc) chemistry and were purified as described previously (Struyf et al., 2001). The bacterial chemotactic peptide fMLP was obtained from Sigma (St. Louis, MO). To measure chemokine production by fibroblasts, THP-1 cells and peripheral blood mononuclear cells (PBMC) cells were stimulated with a diverse set of inducers: recombinant human IFN-γ and IL-1β (both from Peprotech), concanavalin A (ConA; Calbiochem, La Jolla, CA), LPS from Escherichia coli (0111:B4; Difco Laboratories, Detroit, MI), the double-stranded RNA polyriboinosinic:polyribocytidylic acid (polyrI:rC or PIC) and ...
Abe, N; Yamaguchi, T; Hoshino, F; Suzuki, F; Ebina, A; and Ishida, N, "Antitumor and interferon-inducing activities of th69, a whole bacterial preparation of streptococcus faecalis, in mice." (1982). Subject Strain Bibliography 1982. 853 ...
Figure 3. Commonly-used fiber models and in silico base mutations. (A) Six commonly used models highlighted in the Fiber module: single-stranded RNA, double-helical A-, B-, and C-form DNA, the Pauling triplex model (32), and the parallel polyI:polyI:polyI:polyI quadruplex. (B) Single-stranded RNA fiber model of base sequence AUCGAUCGAUCG. (C) Double-helical B-DNA fiber model with sequence ATCGATCGATCG on the leading strand. (D) Pauling triplex model with each strand of sequence AAAACCCCGGGG. (E) parallel polyI:polyI:polyI:polyI quadruplex model with 12 layers of hydrogen-bonded hypoxanthine tetrads. Models in (B-E) were generated using the default settings on the w3DNA 2.0 server, each taking just two mouse clicks. (F) All hypoxanthine bases along the poly I chains mutated to guanine via the Mutation module, leading to a parallel G-quadruplex. Color code for base blocks: A, red; C, yellow; G, green; T, blue; U, cyan; I, dark green ...
Synthetic double-stranded ribopolynucleotides are inducers of interferon, a protein which increases the resistance of cells to virus attack.. This work describes the synthesis of poly (halogenated ribocytidylic acids) and their complex formation with both riboinosinic acid and deoxyriboinosinic acid. The RNA/RNA hybrids are potent interferon inducers with high thermal and nucleolytic stability, the DNA/RNA hybrids are, however, completely inactive . as inducers of interferon.. The synthesis and physical properties of poly (5-hydroxycytidylic . acid) are discussed. In basic solution this polymer undergoes a conformational change and can also bind magnesium ions in an unusual manner. The polymer does not hybridise with polyinosinic acid.. ...
Serum interferon-α is a useful biomarker in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositisSerum interferon-α is a useful biomarker in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis ...
Deciphering a Different Kind of Code. You may have great genes, but if the genes are tightly wrapped up in the proteins that organize DNA into chromosomes, those genes can t be accessed and turned on. Now a regulatory code that controls if an enveloped gene will be active or silent has been deciphered for the first time by P&S researchers.. Cells can get access to genes by pushing the chromosomal proteins, called histones, away from the gene s DNA. But first the cell must decipher a code, which consists of a chemical modification of the histones. Understanding the histone code could lead to therapies that shut down or turn on genes in diseases, such as cancer, that have aberrant patterns of gene expression.. Dr. Dimitris Thanos, associate professor of biochemistry and molecular biophysics, and his postdoctoral researcher, Dr. Theodora Agalioti, cracked the histone code that controls the human beta-interferon gene. The research was published in the Nov. 1, 2002, issue of Cell. Rare Disorders May ...
Whether poly-ICLC vaccination is safe and efficacious for patients with melanoma, head and neck cancer, sarcoma, or a non-melanoma skin cancer.
This trial will investigate the efficacy and tolerability of FLT-3 ligand and poly-ICLC in patients with low grade B-cell lymphomas.
Although germinally transmitted ΔMuDR elements are transcriptionally active and produce chimeric sense/antisense transcripts, they have no measurable impact on mudrA transcript levels or Mu1 TIR methylation. As determined by in situ hybridization, antisense mudrA transcripts colocalized with sense mudrA and mudrB transcripts in many tissues of active Mutator plants, and the sense and antisense transcripts may have been paired in vivo (Joanin et al., 1997).. As with documented cases of quelling in fungi, RNA interference in animals, and cosuppression in transgenic plants (reviewed by Matzke et al., 2001; Vance and Vaucheret, 2001), structural properties of ΔMuDR transcripts would be predicted to lead to RNA-based epigenetic gene silencing (Walbot and Rudenko, 2002). Ectopically expressed antisense RNAs are thought to pair with sense transcripts and feed into the double-stranded RNA-induced degradation pathway (Stam et al., 2000; Van Houdt et al., 2000; Serio et al., 2001), and in such cases, ...
By Kevin E. Noonan -- Today the Federal Circuit reversed a priority determination in an interference over claims to human beta-interferon, in an opinion teeming with irony, déjà vu, anachronism, and the peculiar effects on outcome caused by the form of interference counts. Two interferences, Nos. 105,334 and 105,337 between Junior Party David Goeddel and Robert Crea and Senior Party Haruo Sugano, Masami Muramatsu, and Tadatsigi Tanaguchi, were directed towards claims to isolated human DNA encoding beta-interferon (also termed human fibroblast interferon or hFIF in the opinion) as well as the isolated interferon protein itself. The DNA Interference was declared...