Relevant bibliographies by topics / Ifns

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  2. Dissertations / Theses
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  4. Book chapters
  5. Conference papers
  6. Reports

Academic literature on the topic 'Ifns'

Author: Grafiati
Published: 4 June 2021
Last updated: 5 February 2022

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Journal articles on the topic "Ifns"

1

Bruening, Janina, Bettina Weigel, and Gisa Gerold. "The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy." Journal of Immunology Research 2017 (2017): 1–12. http://dx.doi.org/10.1155/2017/7232361.

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The human interferon (IFN) response is a key innate immune mechanism to fight virus infection. IFNs are host-encoded secreted proteins, which induce IFN-stimulated genes (ISGs) with antiviral properties. Among the three classes of IFNs, type III IFNs, also called IFN lambdas (IFNLs), are an essential component of the innate immune response to hepatitis C virus (HCV). In particular, human polymorphisms in IFNL gene loci correlate with hepatitis C disease progression and with treatment response. To date, the underlying mechanisms remain mostly elusive; however it seems clear that viral infection of the liver induces IFNL responses. As IFNL receptors show a more restricted tissue expression than receptors for other classes of IFNs, IFNL treatment has reduced side effects compared to the classical type I IFN treatment. In HCV therapy, however, IFNL will likely not play an important role as highly effective direct acting antivirals (DAA) exist. Here, we will review our current knowledge on IFNL gene expression, protein properties, signaling, ISG induction, and its implications on HCV infection and treatment. Finally, we will discuss the lessons learnt from the HCV and IFNL field for virus infections beyond hepatitis C.
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2

Khan, O. A., H. Jiang, P. S. Subramaniam, H. M. Johnson, and S. S. Dhib-Jalbut. "Immunomodulating functions of recombinant ovine interferon tau: potential for therapy in mulitple sclerosis and autoimmune disorders." Multiple Sclerosis Journal 4, no. 2 (April 1998): 63–69. http://dx.doi.org/10.1177/135245859800400204.

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The interferons (IFN) are a family of complex proteins possessing antiviral, antiproliferative, and immunomodulatory activities. Two type 1 recombinant human IFN have been recently approved for the treatment of multiple sclerosis (MS). However, use of high dose type 1 IFN treatment in MS patients has been limited by dose-related toxicity. Ovine IFNt is a unique type 1 interferon discovered for its role in the animal reproductive cycle. It differs from other type 1 IFNs in that it is remarkably less toxic even at high concentrations, is able to cross species barriers, and is not inducible by viral infection. Ovine IFNt has been shown to be very effective in the treatment of animal models of MS. In this study, we examined the toxicity of OvIFNt on human T-cells at high doses and its immunregulatory properties at equivalent doses. Our experiments confirmed the remarkably non-toxic nature of OvIFNt on human cells at high concentrations as well as immunomodulating properties consistent with other type 1 IFNs including an antilymphoproliferative effect and inhibition of IFNg-induced HLA class II expression. These results suggest that OvIFNt could be developed into a potentially less toxic therapeutic option for immune-mediated disorders including MS.
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Bauersachs, S., S. E. Ulbrich, H. D. Reichenbach, M. Reichenbach, M. Büttner, H. H. D. Meyer, T. E. Spencer, et al. "83 EFFECTS OF HUMAN INTERFERON-α ON GENE EXPRESSION IN THE BOVINE ENDOMETRIUM IN COMPARISON TO DAYS 15 AND 18 OF PREGNANCY." Reproduction, Fertility and Development 24, no. 1 (2012): 154. http://dx.doi.org/10.1071/rdv24n1ab83.

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Interferon-τ (IFNT), a Type-I interferon (IFN), is the pregnancy recognition signal produced by the ruminant conceptus (Godkin et al. 1984; Hansen et al. 1985; Helmer et al. 1987; Spencer et al. 2007). In addition to these specific functions of IFNT in ruminants, many studies suggest that IFNs play a general role in establishment of pregnancy and conceptus attachment/implantation in most mammalian species (Bazer et al. 2009; Bazer et al. 2010; Johnson et al. 2009; Roberts et al. 2008). To characterise the effects of prototype Type-I IFNs on bovine endometrium, in experiment one, Simmental heifers were treated from Day 14 to Day 16 of the oestrous cycle with a rod-shaped intrauterine device releasing human interferon-α (IFNA) or placebo lipid extrudates or PBS only as controls (n = 4 each). Lipid formulation and concentration of human IFNA were adjusted to release 8–9 × 107 IU of IFNA over a period of 2 days in in vitro release experiments. On Day 16, endometrial biopsy samples were collected after flushing the uterus. In experiment 2, endometrial tissue samples were obtained on Day 12, 15 and 18 post-mating from nonpregnant or pregnant heifers. All samples from both experiments were analysed with an Affymetrix Bovine Genome Array (Santa Clara, CA). In experiment one, IFNA treatment resulted in differential gene expression in the bovine endometrium. Significant differences were found between the IFNA group and both control groups, whereas no differences were observed between the placebo and the PBS control group. In experiment 2, differentially expressed genes were found between pregnant and nonpregnant endometria on Day 15 and 18, but not on Day 12, with many of them known IFN-stimulated genes. The comparison of the data sets from both experiments showed very similar gene expression changes for most of the typical IFN-stimulated genes. In addition, several genes were identified which were differentially expressed after IFNA treatment but not different at Day 15 or 18 of pregnancy compared with nonpregnant animals. Conversely, some genes were found as differentially expressed during pregnancy but not after IFNA treatment. Differential expression of selected genes was verified by quantitative real-time PCR and 4 genes, namely jumonji C domain containing histone demethylase 1 homologue D (JHDM1D), indoleamine 2,3-dioxygenase 1 (IDO1), fatty acid binding protein 3, muscle and heart (mammary-derived growth inhibitor) (FABP3) and dickkopf homologue 1 (DKK1), were selected for localization of mRNA expression in endometrial tissue sections. The findings of this study suggest that there may be differential effects of bovine IFNT compared with human IFNA and that some pregnancy-specific changes in the endometrium are elicited by conceptus-derived factors other than IFNT. This study was supported by the German Ministry for Education and Research (BMBF, FUGATO-plus, COMPENDIUM) and the German Research Foundation (DFG FOR478). The authors are part of the European Union COST action GEMINI.
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4

Shank, Kaitlyn, Yusup Shin, Carson Wills, Nicole Cunningham, Alevtina Domashenko, Russell Garrett, Jenni A. Punt, and Stephen G. Emerson. "IFNs Upregulate Sca-1 and Block Proliferation in Murine Hematopoietic Stem and Progenitor Cells,." Blood 118, no. 21 (November 18, 2011): 3394. http://dx.doi.org/10.1182/blood.v118.21.3394.3394.

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Abstract Abstract 3394 Hematopoietic stem cells (HSC) replenish the cellular components of the blood throughout life by a homeostatic process in which the majority of HSCs remain quiescent while a small percentage enter the cell cycle to either self-review or differentiate. During inflammatory responses to infections, Interferons (IFNa, IFNg) perturb HSC homeostasis, presumably in response to the demand for increased numbers of inflammatory cells. Previous studies have highlighted an apparent paradox, i.e. IFNs suppress the proliferation of normally cycling murine hematopoietic progenitor cells (HPCs), yet increase the fraction of normally quiescent Sca+ HSCs that proliferate. To investigate the mechanisms underlying this paradox, we dissected the dynamics of cell surface phenotypes, cell cycle kinetics, pro- and anti-apoptotic pathways within the HSC and HPC compartments in response to pIpC and IFNs both in vivo and in vitro. Forty-eight hours after pIpC injection, bone marrow (BM) cellularity declined by 60%, the proportion of Sca- kit+ HPCs fell from 0.45% to 0.05%, while the proportion of BM cells with the Sca+ kit+ HSC phenotype increased from 0.17 to 0.26%. To determine whether the increase in Sca+kit+ cells was due to proliferation of HSCs or upregulation of Sca-1 on HPCs, we cultured purified CD150+ Sca-Kit+ HPCs and CD150+Sca+kit+ HSCs in vitro with IFNa, IFNg, or PBS. Sca expression was induced on previously Sca- HPCs, and the level of Sca expression on HSCs was also increased. This induction was detectable as early as 6 hours after treatment and accompanied by an increase in Sca mRNA. BrdU incorporation into both HPC and HSC populations decreased from pre-treatment baselines, further indicating that the increase in cells with the HSC phenotype was not due to HSC proliferation, but rather the appearance of cycling HPCs within the HSC staining gate following IFN-induced upregulation of Sca. Staining with FITC-DEVD-FMK identified active cleaved capase-3 in pIpC- or IFN-treated cells, suggesting that the reduced cellularity following IFN reflected a cellular stress that killed Lin+ precursors cells and some HPCs, but spared HSCs. In contrast to lin+kit- precursors, all kit + HPCs and HSCs expressed bcl-2, suggesting that expression of anti-apoptotic proteins may prevent IFN-induced stress from resulting in HSC/HPC apoptosis despite the initial triggering of caspase-3 cleavage. In summary, acute treatment with IFNs has anti-proliferative effects on all hematopoietic cells, including precursors, HPCs and HSCs, with the apparent increase in HSC proliferation the result of HPCs masquerading as Sca+HSCs after exposure to IFN. Unlike precursors, HSCs and some HPCs survive treatment to IFNs despite activation of cleaved caspase-3, possibly due to their expression of bcl-2, and likely related anti-apoptotic regulators. The previously observed increase in HSC proliferation days and weeks following IFN treatment is most likely due to the homeostatic response of HSCs to the depopulation of the precursor and HPCs caused by acute IFN exposure. Disclosures: No relevant conflicts of interest to declare.
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5

Leavy, Olive. "IFNs boost cancer killers." Nature Reviews Immunology 11, no. 11 (October 25, 2011): 719. http://dx.doi.org/10.1038/nri3094.

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6

Snyder, Deann T., Jodi F. Hedges, and Mark A. Jutila. "Getting “Inside” Type I IFNs: Type I IFNs in Intracellular Bacterial Infections." Journal of Immunology Research 2017 (2017): 1–17. http://dx.doi.org/10.1155/2017/9361802.

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Type I interferons represent a unique and complex group of cytokines, serving many purposes during innate and adaptive immunity. Discovered in the context of viral infections, type I IFNs are now known to have myriad effects in infectious and autoimmune disease settings. Type I IFN signaling during bacterial infections is dependent on many factors including whether the infecting bacterium is intracellular or extracellular, as different signaling pathways are activated. As such, the repercussions of type I IFN induction can positively or negatively impact the disease outcome. This review focuses on type I IFN induction and downstream consequences during infection with the following intracellular bacteria:Chlamydia trachomatis,Listeria monocytogenes,Mycobacterium tuberculosis,Salmonella entericaserovar Typhimurium,Francisella tularensis,Brucella abortus,Legionella pneumophila, andCoxiella burnetii. Intracellular bacterial infections are unique because the bacteria must avoid, circumvent, and even co-opt microbial “sensing” mechanisms in order to reside and replicate within a host cell. Furthermore, life inside a host cell makes intracellular bacteria more difficult to target with antibiotics. Because type I IFNs are important immune effectors, modulating this pathway may improve disease outcomes. But first, it is critical to understand the context-dependent effects of the type I IFN pathway in intracellular bacterial infections.
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Kimura, M., J. A. Majde, L. A. Toth, M. R. Opp, and J. M. Krueger. "Somnogenic effects of rabbit and recombinant human interferons in rabbits." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 267, no. 1 (July 1, 1994): R53—R61. http://dx.doi.org/10.1152/ajpregu.1994.267.1.r53.

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Interferons (IFNs) are antiviral cytokines that possess several central nervous system activities. IFN therapy is associated with sleepiness, and the IFNs expressed during viral infection may be involved in the excess sleep associated with these infections. Most viruses stimulate the production of both IFN-alpha and IFN-beta. Although large doses of human IFN-alpha 2 are somnogenic in rabbits, the effects of species-specific IFNs on sleep in the rabbit have not been documented. We compared the somnogenic and antiviral effects of IFNs derived from rabbits to the effects of recombinant human (rh) IFN-alpha and IFN-beta. When injected intracerebroventricularly, rhIFN-alpha A/D, rabbit IFN-alpha/beta, and rabbit reference IFN induced non-rapid-eye-movement sleep and fever in a dose-dependent manner. However, the doses of rabbit IFNs required to induce sleep were much lower than those of human IFNs. Heat treatment of both rabbit IFNs and human IFNs greatly reduced their in vitro antiviral effects. The in vivo activities of rabbit IFNs and rhIFN-alpha A/D were significantly attenuated after heat treatment. However, rhIFN-beta retained its sleep-promoting action after heat treatment, suggesting that microbial contaminants were responsible for its somnogenic and pyrogenic activities. We conclude that IFN-alpha is somnogenic.
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Chandrasekaran, Sanjay, Maiko Sasaki, and Brian Paul Pollack. "PTEN/PI3K signaling in cancer and the response to cytokines: From growth factors to immune actors." Journal of Clinical Oncology 37, no. 8_suppl (March 10, 2019): 35. http://dx.doi.org/10.1200/jco.2019.37.8_suppl.35.

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35 Background: The PTEN/PIK3 pathway plays an important role in the cellular response to growth factors and aberrant activation of PI3K signaling is a hallmark of many forms of cancer. While the role of PI3K signaling has been well studied in the context of growth factor biology, its role in the cellular response to cytokines such as interferons (IFNs) is less well understood. We examined the impact of PI3K activation on interferon signaling pathways using an in vitro experimental model system. Methods: Cultured human HCT 116 colorectal carcinoma cells and isogenic PTEN (-/-) cells were treated with escalating doses of IFNg, IFNa2b, and IFNl. IFN response was evaluated by measuring MHC Class I and Class II mRNA levels and cell surface expression via RT-PCR and flow cytometry, respectively. Western blots for total AKT, phospho-AKT (pAKT), PTEN, STAT1, and pSTAT1 were performed. Corroborating pharmacologic studies were performed using cultured HPV-negative SqCC/Y1 oSCC cells treated with IFN and the PTEN inhibitor VO-OHpic and AKT activator SC79. Clinical correlates utilizing immunohistochemistry (IHC) on human head and neck cancers were conducted. Results: PTEN (-/-) cells expressed lower basal levels of MHC I and the induction by IFNs were likewise attenuated. Dramatically, PTEN knockout reduced IFN-g- induced surface expression of MHC II by > 50%. Corresponding reductions in MHC I/II mRNA were seen. IHC in patient biopsy samples showed an inverse relationship between phospho-AKT and MHC I expression. We identified a potential explanation of this effect wherein PTEN/PIK3 signaling implicates STAT1, a downstream target of IFN signaling. PTEN inhibition consistently modulated total and phosphorylated levels of STAT1 protein. Conclusions: Much remains unknown about the link between growth factor pathways and the tumor immune response. We demonstrate using an in vitro model that genetic and pharmacologic activation of the PI3K pathway attenuates the immune response to IFNs and represses MHC induction and expression. We present a novel mechanism for explaining this phenomenon linking the PTEN/PIK3 and STAT1 pathways. Further characterization of this interaction in in vitro models is necessary.
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Abdolvahab, Mohadeseh Haji, Behrad Darvishi, Mohammad Zarei, Keivan Majidzadeh-A, and Leila Farahmand. "Interferons: role in cancer therapy." Immunotherapy 12, no. 11 (August 2020): 833–55. http://dx.doi.org/10.2217/imt-2019-0217.

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Interferons (IFNs) are a group of signaling cytokines, secreted by host cells to induce protection against various disorders. IFNs can directly impact on tumor cells or indirectly induce the immune system to protect host cells. The expression levels of IFNs and its functions of are excellently modulated in a way to protect host cells from probable toxicities caused by extreme responses. The efficacy of anticancer therapies is correlated to IFNs signaling. Although IFN signaling is involved in induction of antitumor responses, chronic stimulation of the IFN signaling pathway can induce resistance to various antineoplasm therapies. Hence, IFNs are expressed by both cancer and immune cells, and modulate their biological function. Understanding this mechanism of action might be a key target of combination therapies.
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Chen, Yongzhi, Xuqiu Lei, Zhaozhao Jiang, and Katherine A. Fitzgerald. "Cellular nucleic acid–binding protein is essential for type I interferon–mediated immunity to RNA virus infection." Proceedings of the National Academy of Sciences 118, no. 26 (June 24, 2021): e2100383118. http://dx.doi.org/10.1073/pnas.2100383118.

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Type I interferons (IFNs) are innate immune cytokines required to establish cellular host defense. Precise control of IFN gene expression is crucial to maintaining immune homeostasis. Here, we demonstrated that cellular nucleic acid–binding protein (CNBP) was required for the production of type I IFNs in response to RNA virus infection. CNBP deficiency markedly impaired IFN production in macrophages and dendritic cells that were infected with a panel of RNA viruses or stimulated with synthetic double-stranded RNA. Furthermore, CNBP-deficient mice were more susceptible to influenza virus infection than were wild-type mice. Mechanistically, CNBP was phosphorylated and translocated to the nucleus, where it directly binds to the promoter of IFNb in response to RNA virus infection. Furthermore, CNBP controlled the recruitment of IFN regulatory factor (IRF) 3 and IRF7 to IFN promoters for the maximal induction of IFNb gene expression. These studies reveal a previously unrecognized role for CNBP as a transcriptional regulator of type I IFN genes engaged downstream of RNA virus–mediated innate immune signaling, which provides an additional layer of control for IRF3- and IRF7-dependent type I IFN gene expression and the antiviral innate immune response.
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Dissertations / Theses on the topic "Ifns"

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Gongora, Céline. "Identification et caractérisation d'un nouveau gène induit par les IFNs : isg20." Montpellier 2, 1999. http://www.theses.fr/1999MON20082.

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Nous venons d'identifier par criblage differentiel un nouveau gene induit par les interferons (ifns). L'etude de ce gene, isg20, a constitue la base de mon projet de these. Nous avons d'abord montre que la proteine isg20 se localise dans des complexes multiproteiques associes a la matrice nucleaire appeles corps pml. Ces corps jouent probablement un role dans la reponse antivirale mediee par les ifns puisqu'une grande partie des proteines contenues dans ces corps sont inductibles par l'ifn et qu'ils sont destructures apres infection virale. Nous venons d'obtenir des anticorps monoclonaux contre isg20, ce qui nous permettra de suivre sa localisation cellulaire apres infection virale. La presence d'un domaine proteique caracteristique de proteines possedant une activite adn ou arn exonuclease 3-5 sur la proteine isg20, nous a conduit a montrer qu'isg20 possedait une activite exonuclease. Enfin, tres recemment, isg20 a ete identifie par un autre groupe comme un nouveau gene modulable par les oestrogenes. De plus, isg20 semble induit par le vih. Le clonage du promoteur du gene isg20 que nous venons de realiser nous a permis d'etudier sa regulation, notamment par les ifns, les oestrogenes et le vih.
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Naujoks, Jan. "Type I and II IFNs modify the proteome of bacterial vacuoles to restrict infections via IRG1." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2015. http://dx.doi.org/10.18452/17367.

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Die hier vorgestellte Studie untersucht systematisch die angeborene Immunabwehr gegen L. pneumophila auf Ebene des gesamten Wirtsorganismus, sowie auf molekularer Ebene in Alveolar- und Knochenmarksmakrophagen. Mittels in vivo Transkriptomanalysen werden Typ I und II Interferone (IFN) als Hauptregulatoren der frühen pulmonalen Genexpression in der L. pneumophila-Infektion identifiziert. Infektionsexperimente in Wildtyp- und IFN-Rezeptor-defizienten Tieren offenbaren, dass Typ I und II IFNe maßgeblich die antibakterielle Abwehr gegen L. pneumophila vermitteln. Für die Bekämpfung der Infektion in der Lunge werden CD11c+ Zellen als wichtigste Empfänger der IFN-Signale identifiziert. Des Weiteren wird durch Behandlung von CD11c+ Alveolarmakrophagen mit IFNen ex vivo das intrazelluläre bakterielle Wachstum inhibiert. Mittels subzellulärer quantitativer Massenspektrometrie wird gezeigt, dass die Proteinkomposition der Legionellen-enthaltenden Vakuole substanziell durch beide IFNe modifiziert wird. In einer vergleichenden Netzwerkanalyse werden diese Proteomdaten mit eigenen und öffentlich zugänglichen Transkriptomdaten verglichen. Hierdurch können klar abgegrenzte Untergruppen von einerseits transkriptionell durch IFN-regulierten Proteinen sowie andererseits ausschließlich räumlich IFN-regulierten Proteinen unterschieden werden. Unter den durch IFN an der Vakuole angereicherten Proteinen wird Immunoresponsive gene 1 (IRG1) als zentraler Effektor identifiziert, welcher das Wachstum von L. pneumophila durch die Produktion des antibakteriellen Metaboliten Itaconsäure inhibiert. Zusammenfassend stellt diese Studie eine umfassende Ressource von IFN-vermittelten Effekten auf die Genexpression sowie auf das Proteom der bakteriellen Vakuole dar und deckt einen zellautonomen Abwehrmechanismus gegen L. pneumophila auf, welcher durch die IRG1-abhängige Produktion von Itaconsäure vermittelt wird.
The study presented here systemically examines the innate immune response against L. pneumophila on whole organism level as well as on a molecular level within macrophages, L. pneumophilas’ host cell. In vivo transcriptome analyses identify type I and II interferons (IFNs) as master regulators of the early pulmonary gene expression during L. pneumophila infection. Infection experiments in wild-type mice and mice lacking type I and/or II IFN signaling reveal a severe defect of antibacterial defense when IFN signaling is absent. CD11c+ cells were found to be the main targets of IFNs to restrict infection in the lung, and IFNs inhibited bacterial growth in CD11c+ alveolar macrophages ex vivo. Subcellular quantitative mass spectrometry shows that both IFNs substantially modify the protein composition of Legionella-containing vacuoles. Comparative network analysis, combining these proteome data with transcriptome data as well as public database data reveals distinct subsets of transcriptionally regulated IFN-stimulated genes (ISGs) on the one hand, but interestingly also exclusively spatially IFN-regulated vacuolar proteins. Among IFN-regulated vacuolar proteins, Immunoresponsive gene 1 (IRG1) was identified as a central effector that restricts growth of L. pneumophila through production of the antibacterial metabolite itaconic acid in macrophages. Collectively, this study provides a comprehensive resource of IFN-mediated effects on gene expression and the bacterial vacuolar proteome, and uncovers a cell-autonomous defense pathway against L. pneumophila, which is mediated by IFNs, IRG1 and itaconic acid.
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Zanin, Natacha. "Role de STAM dans la régulation endosomale de la signalisation JAK/STAT induite par les IFNs." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS047.

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La première implication des récepteurs aux interférons de type 1 (IFNAR1) dans le contrôle de la voie Jak/STAT induite par les IFNs a été établie par mon laboratoire il y a une dizaine d'années (Marchetti et al., 2006). Une des questions fondamentales était alors de déterminer comment et pourquoi l'endocytose des IFNARs pouvait contrôler la voie Jak/STAT. Deux acteurs clés du tri endosomal ont attiré notre attention : Hrs (Hepatocyte growth factor-Regulated tyrosine kinase Substrate) et STAM (Signal Transducing Adaptor Molecule). Ces deux protéines constituent le complexe ESCRT-0 (Endosomal Sorting Complexes Required for Transport-0) les localisant, de manière idéale, à l'interface entre signalisation cellulaire et trafic membranaire.La combinaison de la biologie moléculaire et cellulaire, de la biochimie et de la microscopie à fluorescence, nous a permis d'établir que STAM s'associe au complexe IFNAR1 à la membrane plasmique afin d'y exercer son effet inhibiteur sur la signalisation Jak/STAT. Cette inhibition est levée lorsqu'IFNAR est libéré dans l'endosome et qu'il peut ainsi être recruté par Hrs sous la dépendance de l'IFN-α. En nous basant sur des expériences de déplétion par shRNA ou d'inhibition pharmacologique, nous avons identifié PTP1B (Protein Tyrosine Phosphatase 1B) en tant qu'activateur de la voie Jak/STAT induite par les IFNs. Le blocage sélectif de l'endocytose d'IFNAR par déplétion de clathrin, nous a permis de montrer que l'activation de PTP1B est inhibée à la membrane plasmique. Cela a été confirmé par des expériences d'interaction protéine-protéine (Proximity Ligation Assay) indiquant que STAM est constitutivement associé à IFNAR1, tandis que l'interaction entre IFNAR1 et Hrs a seulement lieu à l'endosome.Ainsi, nos résultats permettent d'établir un modèle dans lequel, à la membrane plasmique, STAM est un frein permanent à la signalisation Jak/STAT, qui est levé après l'endocytose d'IFNAR et sa libération dans l'endosome de tri. De plus, nous avons montré que l'interaction Hrs/STAM dans l'endosome précoce permet de différencier, de manière sélective, l'activation de la signalisation Jak/STAT médiée par l'IFN-α ou l'IFN-β
A decade ago, my laboratory established the first role of type I IFNs receptor (IFNAR) endocytosis in the control of Jak/STAT signaling induced by type 1 IFNs (Marchetti et al., 2006). A salient question is now to elucidate why and how IFNAR endocytosis could control the Jak/STAT pathway. Two key players of endosomal sorting retained our interest: Hrs (Hepatocyte growth factor-Regulated tyrosine kinase Substrate) and STAM (Signal Transducing Adaptor Molecule). These two classical components of the ESCRT-0 (Endosomal Sorting Complexes Required for Transport-0) complex were ideally placed at the interface between signaling and membrane trafficking. By using a combination of molecular and cellular biology, biochemistry, and fluorescent microscopy, we could establish that STAM binds to the IFNAR complex at the plasma membrane to exert an inhibitory effect on Jak/STAT signaling. This inhibition is removed when IFNAR is delivered to the sorting endosome by interacting with Hrs upon IFN-α stimulation. Based on shRNA down-expression and pharmacological inhibition, we further involve the PTP1B (Protein Tyrosine Phosphatase 1B) as it activates Jak/STAT signaling upon IFN stimulation. We could also show that PTP1B activation is inhibited by STAM at the plasma membrane from experiments where IFNAR endocytosis was blocked by siRNA-mediated clathrin down-expression. This was further confirmed by protein-protein interaction experiments (Proximity Ligation Assay) showing that STAM was constitutively associated with IFNAR1, whereas the interaction between IFNAR1 and Hrs occured only at the sorting endosome. Our results therefore allow to draw a model where STAM is a constitutive handbrake on Jak/STAT signaling at the plasma membrane that is released after IFNAR endocytosis and delivery to the sorting endosome. We further show that Hrs/STAM interaction at the early endosome allows to selectively distinguish the activation of Jak/STAT signaling mediated by IFN-α or IFN-β
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Gerarduzzi, Casimiro. "Poly IC induced antiviral responses of type I IFNs alter thymopoietic processes in mice : an apoptotic liaison." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97960.

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Type I IFNs modulate the onset of immune responses against viruses through the activation of numerous rapid signaling pathways. Although beneficial on specific infected cells, administered IFNs were shown to decrease thymic cellularity. Herein, we developed a murine model treated with polyinosinic:polycytidylic acid (Poly IC) to dissect the mechanisms and the role of in vivo produced IFNs on the thymus. Treatment induced thymic atrophy, while having no effect on the lymph nodes. However, under chronic conditions, we observed a complete thymic replenishment. These findings should be the result of a LPS contamination, since the use of a new certified LPS-free Poly IC induced a maintained thymic atrophy in time. DP (CD4+CD8+) cells were mostly affected, where part of this decrease was contributed by apoptosis. T cell receptor excision circle (TREC) levels, produced during T cell receptor (TCR) rearrangements, were unaffected, suggesting no alteration of this diversity factor. Additionally, measured up-regulation of MHC class I expression could result in aberrant thymic selections with a modification of selection ranges. Finally, using Caspase 3 KO mice, we showed that DP apoptosis was Caspase-3 independent.
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5

Liu, Qinfang. "Interaction of type I interferons and mTOR signaling underlying PRRSV infection." Thesis, Kansas State University, 2016. http://hdl.handle.net/2097/32860.

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Master of Science in Biomedical Sciences
Department of Anatomy and Physiology
Yongming Sang
Animal metabolic and immune systems integrate and inter-regulate to exert effective immune responses to distinct pathogens. The signaling pathway mediated by mechanistic target of rapamycin (mTOR) is critical in cellular metabolism and implicated in host antiviral responses. Recent studies highlight the significance of the mTOR signaling pathway in the interferon (IFN) response. Type I IFNs mediate host defense, particularly, against viral infections, and have myriad roles in antiviral innate and adaptive immunity. In addition to their well-known antiviral properties, type I IFNs also affect host metabolism. However, little is known about how animal type I IFN signaling coordinates immunometabolic reactions during antiviral defense. Therefore, understanding the interaction of mTOR signaling and the type I IFN system becomes increasingly important in potentiating antiviral immunity. Tissue macrophages (MФs) are a primary IFN producer during viral infection, and their polarization to different activation statuses is critical for regulation of immune and metabolic homeostasis. Using porcine reproductive and respiratory syndrome virus (PRRSV) as a model, we found that genes in the mTOR signaling pathway were regulated differently in PRRSV-infected porcine alveolar MФs at different activation statuses. Therefore we hypothesize that: 1) the mTOR signaling pathway involves host anti-PRRSV regulation; 2) mTOR signaling interacts with IFN signaling to modulate the antiviral response; and 3) different type I IFN subtypes (such as IFN-α1 and IFN-β) regulate mTOR signaling differently. We show that modulation of mTOR signaling regulated PRRSV infection in MARC-145 cells and porcine primary cells, in part, through regulating production and signaling of type I IFNs. In addition, expression and phosphorylation of two key components in the mTOR signaling pathway, AKT and p70 S6 kinase, were regulated by type I IFNs and PRRSV infection. Taken together, we determined that the mTOR signaling pathway, a key pathway in regulation of cell metabolism, also mediates the type I IFN response, a key immune response in PRRSV infection. Our findings reveal that the mTOR signaling pathway potentially has a bi-directional loop with the type I IFN system and implies that some components in the mTOR signaling pathway can serve as targets for augmentation of antiviral immunity and therapeutic designs.
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6

Aggad, Dina. "Diversité des interférons et de leurs récepteurs chez le Danio rerio." Montpellier 2, 2009. http://www.theses.fr/2009MON20117.

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Les IFNs sont un groupe de cytokines définis par leur activité antivirale. Chez les mammifères, ils sont divisés en trois groupes. Ils fixent tous des complexes récepteurs distincts et possèdent une structure génique différente. Les types I (principalement α et β) ont un seul exon, le type II (γ) quatre exons et le type III (λ) cinq. Les types I et III constituent un sous-groupe connu sous le nom « d'IFNs induits par les virus », car ils sont directement induits par une infection virale, alors que le type II ne l'est pas. La présence d'IFN induits par les virus et d'IFNγ (possédant 4 exons) ont été signalé dans toute les études poussées chez les poissons, la plupart, sinon tous, possèdent plusieurs gènes codant pour ces IFNs. La classification des IFNs induits par les virus chez les poissons est très controversée, nous avons pris parti de les nommer IFNφ (possédant 5 exons). Au cours de cette thèse nous avons identifié un IFN en plus appartenant aux IFNφs, nous avons caractérisé les propriétés des IFNφs et IFNγs et nous avons identifié leurs complexes récepteurs in vivo. Le génome du danio code pour 4 IFNφs et 2 IFNγs, nous avons montré que l'expression et le profil d'induction de ces IFNs sont différents, qu'ils possédaient une activité biologique antivirale et que les IFNφs étaient capables de protéger contre l'infection virale. Finalement l'utilisation d'expériences de perte et de gain de fonction, nous ont permis d'identifier les composants transmembranaires des complexes récepteurs
Interferons are a group of cytokines defined by their antiviral activities. In mammals, IFNs are divided into three groups according to their receptor usage. In addition to using distinct receptor complexes, the three mammalian types of IFN also have distinct genetic structure: type I (mainly α and β ) IFN genes have a single exon, type II (γ) IFNs have four exons, while type III (λ) IFNs have five. Type I and type III IFNs together constitute a distinct subgroup known as “virus-induced IFNs” as they are directly induced by viral infections while type II is not. Virus-induced fish IFNs and IFN γ (with 4 exons) have now been reported in all deeply studied fish species; most, if not all, teleost species possess several genes encoding these IFNs. The classification of fish virus-induced IFNs remains controversial, we took advantage of naming IFNφ (with 5 exons). In this work we identified a fourth IFN, which belongs to IFNφs, we characterized the properties of IFNφs and IFNγs and we have found their receptor complexes in vivo. The danio genome encodes 4 IFNφs and 2 IFNγs, we showed that the expression profile and induction of these IFNs are different, they possess antiviral biological activity and the IFNφs were able to protect against the viral infection. Using loss of function and gain of function analysis, we finally identified the transmembrane components of their receptor complexes
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7

Naujoks, Jan Verfasser], Bastian [Akademischer Betreuer] Opitz, Thomas F. [Akademischer Betreuer] [Meyer, and Bernd [Akademischer Betreuer] Lepenies. "Type I and II IFNs modify the proteome of bacterial vacuoles to restrict infections via IRG1 / Jan Naujoks. Gutachter: Bastian Opitz ; Thomas F. Meyer ; Bernd Lepenies." Berlin : Lebenswissenschaftliche Fakultät, 2015. http://d-nb.info/1079901205/34.

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Sales, Paula Cristiane Motta. "Regulação da expressão da proteína cinase PKR na ausência de interferons (IFNs) e seu papel na resposta celular mediada por agonistas dos receptores TLR2 e TLR4." Universidade Federal de Minas Gerais, 2012. http://hdl.handle.net/1843/BUOS-9L7NEM.

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The role of protein kinase R (PKR) in the antiviral cell state induced by interferons (IFNs) is well known. The increase in its expression in response to stimulation by IFNs results in its autophosphorylation and phosphorylation of its substrate eIF2-alpha. This molecular event interferes with translation initiation of mRNA, which in turn results in inhibition of protein synthesis. Recent studies suggest the involvement of PKR in bacterial infections. However, how PKR is activated and what is its biological role in these infections is still largely unexplored. Thus, the central objective of our study was to examine the regulation of expression of PKR in the signaling pathway triggered by agonists of TLR2 and TLR4 in a human promonocytic, THP-1. THP-1 monocytes were treated with LPS (TLR4 agonist) or Pam3CSK4 (TLR2 agonist) in increasing doses or at different time intervals. At the end of these treatments, total RNA and protein extracts were obtained for analysis of the relative abundance of mRNA PKR by real time PCR and protein levels by western blot assays, respectively. The results showed a significant increase in the levels of mRNA PKR and PKR protein. Surprisingly, we did not observe any increase in the levels of transcripts of IFN-beta or subtypes of IFN-alpha. Moreover, treatment of THP-1 cells with LPS or Pam3CSK4 did not result in STAT1 phosphorylation. Supernatants taken from THP-1 cells treated with LPS or Pam3CSK4 did not caused the activation of PKR or ISG56 promoters in reporter gene assays carried out in HEK293T cells. These results provide evidence that in THP-1 monocytes exposed to stimulation with TLR4 and TLR2 agonists, neither transcriptional activation nor production of type I IFNs is observed, and therefore the PKR expression occurs in the absence of IFNs. Once the promoter region of PKR contains other regulatory elements as candidates for its expression regulation, including NF-IL6, NF-kB, Sp1 and Sp3, we decided to assess the effect of three pharmacological inhibitors. The pretreatment of the THP-1 cells with TPCK or Bay11 7082, pharmacological inhibitors of the transcription factor NF-B, inhibited the PKR expression induced by bacterial agonists. The same was observed when cells were pretreated with Mithramycin, an inhibitor of Sp1/Sp3 transcription factor. However, analysis of the phosphorylation of STAT1 in THP-1 cells differentiated to macrophages suggests the involvement of IFNs in cells treated with the TLR4 agonist, but not with TLR2. The monocytes are one of the major cells of the innate immune responses and are essential for host defense against a wide range of pathogens, having an important role in sepsis. We analyzed and compared the survival of WT and PKR-/-polymicrobial sepsis model. The results indicated that PKR appears to play a detrimental role to the host, as PKR-deficient mice survive from sepsis. Our results demonstrate that PKR expression in human monocytes stimulated with bacterial agonists TLRs occurs independently of IFNs, and that the regulatory mechanisms of its expression involve transcription factors that are critical in the inflammatory response. Furthermore, results obtained from the experiments in vivo demonstrate that PKR is an important target for studies of sepsis. Therefore, our study provides new insight into the mechanisms of transcriptional activation of PKR and its role on the innate immune response against bacterial pathogens.
O papel da proteína cinase dependente de RNA de dupla fita (PKR) no estado celular antiviral induzido por interferons (IFNs) é bastante conhecido. O aumento de sua expressão em resposta à estimulação por IFNs pode resultar em sua autofosforilação levando à fosforilação de seu substrato eIF2-alfa. Este evento molecular interfere no início da tradução do mRNA, que por sua vez resulta em inibição da síntese protéica. Estudos recentes sugerem o envolvimento de PKR em infecções bacterianas. No entanto, como PKR é ativada e qual é o seu papel biológico nessas infecções é ainda pouco explorado. Assim, o objetivo central do nosso trabalho foi examinar a regulação da expressão da proteína cinase PKR na via de sinalização disparada por agonistas dos receptores TLR2 e TLR4 em uma linhagem promonocítica humana THP-1. Monócitos THP-1 foram tratados com LPS (agonista de TLR4) ou Pam3CSK4 (agonista de TLR2) em doses crescentes ou em diferentes intervalos de tempo. Ao final desses tratamentos, o RNA total e extratos protéicos foram obtidos para análise da abundância relativa do mRNA de PKR por PCR em tempo real e de seus níveis protéicos por ensaios de western-blot, respectivamente. Os resultados mostram um aumento significativo dos níveis do mRNA e protéicos de PKR. De modo surpreendente, não foi observado qualquer aumento nos níveis dos transcritos de IFN-beta ou dos subtipos de IFN-alfa. Além disso, o tratamento das células THP-1 com LPS ou Pam3CSK4 não resultou na fosforilação de STAT1. Os sobrenadantes das células THP-1 tratadas com LPS ou Pam3CSK4 não acaretaram na ativação dos promotores de PKR ou ISG56 em ensaios de gene repórter conduzidos em células HEK293T. Esses resultados fornecem vidências que em monócitos THP-1 expostos à estimulação com agonistas TLR2 e TLR4 não ocorre a ativação transcricional nem tanto a produção de IFNs do tipo I, e que portanto, a expressão de PKR ocorre na ausência de IFNs. Uma vez que a região promotora de PKR contém outros elementos regulatórios candidatos para sua regulação como NF-IL6, NF-kB, Sp1 e Sp3, decidimos avaliar o efeito de três inibidores farmacológicos. O pré-tratamento das células THP-1 com TPCK ou com Bay11-7082, inibidores farmacológicos do fator de transcrição NF-B, inibiu a expressão de PKR induzida pelos agonistas bacterianos. O mesmo foi observado quando as células foram pré-tratadas com Mitramicina, um inibidor do fator de transcrição Sp1/Sp3. No entanto, análises da fosforilação de STAT1 em células THP-1 diferenciadas a macrófagos sugerem a participação de IFNs em células tratadas com o agonista de TLR4, mas não com TLR2. Os monócitos são uma das principais células da resposta imune inata sendo essenciais para defesa do hospedeiro contra uma gama de patógenos, tendo papel importante na septicemia. Assim, avaliamos e comparamos a sobrevivência de camundongos WT e PKR-/- em modelo de sepse polimicrobiana. Os resultados revelaram que PKR parece ter um papel prejudicial ao hospedeiro, uma vez que a deficiência de PKR impede que os camundongos sucumbam à sepse grave. Nossos resultados demonstram que a expressão de PKR em monócitos humanos estimulados com agonistas TLRs bacterianos ocorre de modo independente de IFNs, e que os mecanismos de regulação de sua expressão envolvem fatores de transcrição críticos da resposta inflamatória. Além disso, os resultados obtidos de experimentos in vivo demonstram que PKR é um importante alvo para estudos de septicemia. Portanto, nosso estudo fornece uma nova visão sobre os mecanismos de ativação transcricional de PKR e de seu papel sobre a resposta imune inata contra componentes bacterianos.
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Naujoks, Jan [Verfasser], Bastian Akademischer Betreuer] Opitz, Thomas F. [Akademischer Betreuer] [Meyer, and Bernd [Akademischer Betreuer] Lepenies. "Type I and II IFNs modify the proteome of bacterial vacuoles to restrict infections via IRG1 / Jan Naujoks. Gutachter: Bastian Opitz ; Thomas F. Meyer ; Bernd Lepenies." Berlin : Lebenswissenschaftliche Fakultät, 2015. http://d-nb.info/1079901205/34.

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Fernández, Bustamante Marta. "Implicación de la vía del TLR4 y de la vía de los IFNs de tipo I y los monocitos en la respuesta clínica a interferón-beta en pacientes con esclerosis múltiple." Doctoral thesis, Universitat Autònoma de Barcelona, 2014. http://hdl.handle.net/10803/285369.

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Introducción: El interferón-beta (IFN-β) se utiliza como tratamiento para los pacientes con esclerosis múltiple remitente-recurrente (EMRR). A pesar de su probada eficacia, un considerable porcentaje de pacientes no responden al tratamiento. Estudios previos realizados en nuestro grupo apuntaron a que la vía de los IFNs de tipo I y la vía de los TLRs podrían estar implicadas en la respuesta al tratamiento. Además, se observó que la población celular responsable de la sobre-activación de la vía de los IFNs de tipo I eran los monocitos. Objetivo: Estudiar la implicación de la vía del TLR4 y la vía de los IFNs de tipo I en la respuesta a IFN-β en pacientes con esclerosis múltiple remitente recurrente (EMRR) y caracterizar el perfil transcriptómico de los monocitos periféricos según su respuesta al tratamiento con IFN-β. Materiales y métodos: Se incluyeron pacientes con EMRR tratados con IFN-β y clasificados como respondedores (R) o no respondedores (NR) según su respuesta clínica. Mediante citometría de flujo, se determinó la expresión extracelular de TLR2, TLR4 e IFNAR1 en monocitos CD14+ de estos pacientes. Se analizó también la expresión de genes pertenecientes a la vía del TLR4 y a la vía de los IFNs de tipo I en células mononucleares de sangre periférica. Además, se realizaron microarrays de expresión de monocitos aislados por sorting. Por otro lado, se realizó un estudio genético donde se testaron SNPs localizados en genes de la vía de los IFNs de tipo I y de la vía de los TLRs. Resultados y conclusiones: En cuanto a la vía de los IFNs de tipo I, se observó que el IFN1b endógeno estaba elevado en pacientes NR. Además, IFNAR1, estaba más presente en monocitos de pacientes NR respecto a los R. Por otro lado, el estudio transcriptómico de los monocitos aislados reveló que una de las vías más diferencialmente expresadas entre los dos subgrupos de pacientes era la de los IFNs de tipo I, cuyos genes se encontraban más expresados en NR. Además de la vía de los IFNs de tipo I, otras vías de señalización se encontraban más activadas en los monocitos de pacientes NR. Entre ellas destacan la disfunción mitocondrial, la síntesis proteica y el inmunoproteasoma, todas ellas relacionadas con los IFNs de tipo I. Todos estos hallazgos se encontraron en muestras recogidas antes del inicio al tratamiento. Al estudiar el efecto del IFN-β exógeno, también se observaron diferencias en la expresión de IFN1b entre los R y los NR, tanto ex vivo como in vitro. El IFN-β exógeno indujo la expresión de IFN1b en pacientes R, efecto que no ocurría en pacientes NR. En cuanto a la vía del TLR4, se obtuvo una menor expresión de TLR4 en monocitos del grupo global de pacientes con EMRR respecto a los controles sanos que además correlacionaba con la escala de discapacidad. El tratamiento de un año con IFN-β indujo la expresión de genes de la vía de los TLRs. Es más, aumentó la presencia de TLR4 en la superficie celular de monocitos. Sin embargo, este efecto es independiente de la respuesta clínica al tratamiento por lo que no parece ser determinante en cuanto a la efectividad clínica del mismo. Por otro lado, se encontraron diferencias entre R y NR en la expresión basal de IRAKM, un regulador negativo de la vía Myd88 dependiente. Por último, en el estudio farmacogenético no se validó ningún SNP como marcador genético de respuesta clínica al tratamiento con IFN-β.
Introduction: Recombinant IFN-β is widely used as a treatment for relapsing-remitting multiple sclerosis (RRMS). Although its efficacy has been demonstrated, some patients do not respond to the treatment. Previous studies performed by our group pointed out that type I IFNs pathway and TLR4 pathway might be implicated in the response to the treatment. Additionally, monocytes from patients that do not respond to treatment showed over-activation of STAT1, which is the transcription factor of type I IFNs pathway. Objective: The aim of this thesis is to investigate the implication of TLR4 pathway and type I IFNs pathway in the response of IFN-β in RRMS patients and to characterize the transciptomic profile of peripheral monocytes depending on the clinical response to IFN-β treatment. Materials and methods: RRMS patients included in this study were treated with IFN-β during two years and were classified into responders (R) or non-responders (NR) based on clinical criteria. Extracellular expression of TLR2, TLR4 and IFNAR1 in CD14+ monocytes was determined by flux cytometry. Also, the expression of genes belonging TLR4 and type I IFN pathways was determined in peripheral blood mononuclear cells. The monocyte population was purified from PBMC and differential gene expression between groups was evaluated using oligonucleotide microarrays. Finally, a pharmacogenetic study was performed by genotyping SNPs located in genes belonging to type I IFNs and TLR4 pathways. Results and conclusions: The study of type I IFN pathway revealed that endogenous IFN1b was elevated in NR patients. Also, its receptor, IFNAR, was more expressed in monocytes’ cell surface from NR. Moreover, the transcriptomic study of purified monocytes showed that one of the most differentially expressed pathways between R and NR was the type I IFNs pathway, which genes were more expressed in NR. Apart from the type I IFNs pathway, other signaling pathways related with it, were more activated in the isolated monocytes from NR patients. Among them, mitochondrial dysfunction, protein synthesis and immunoproteosome were found differentially expressed between two groups of MS patients. This outcome was obtained from patients’ samples collected at basal time, before IFN-β treatment was initiated. When studying the effect of exogenous IFN-β, differences were also observed in IFN1b expression between R and NR, at both ex vivo as in vitro level. Monocytes from global RRMS patients expressed lower levels of TLR4 when compared with healthy controls. Besides, this outcome was correlated with disability scale. The first year of treatment with IFN-β induced the expression of genes belonging to TLR4 pathway. Moreover, it increased the presence of TLR4 in the cell surface of monocytes. However, this effect was independent on the clinical response to the treatment. Differences between R and NR were found in the basal expression of IRAKM, a negative regulator of Myd88 dependent pathway. Finally, the pharmacogenetic study did not validate any SNP as genetic marker of clinical response to the IFN-β treatment.
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Books on the topic "Ifns"

1

Cortes, María Mercedes Anton. Ifni. [Spain]: Incipit Editores, 1996.

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Williams, Cen. Rhys Ifans. Caerdydd: Cyhoeddiadau Relay, 2000.

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Theile, Carsten. Übungsbuch IFRS. Wiesbaden: Gabler Verlag, 2011. http://dx.doi.org/10.1007/978-3-8349-6833-3.

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Theile, Carsten, Michael Becker, Nina Glaesmann, Kai Udo Pawelzik, Daniel von Pigage, and Willi Pretzer. Übungsbuch IFRS. Wiesbaden: Gabler, 2007. http://dx.doi.org/10.1007/978-3-8349-9319-9.

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Theile, Carsten. Übungsbuch IFRS. Wiesbaden: Springer Fachmedien Wiesbaden, 2014. http://dx.doi.org/10.1007/978-3-658-02258-7.

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Christian, Dieter, and Norbert Lüdenbach, eds. IFRS Essentials. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2012. http://dx.doi.org/10.1002/9781119207917.

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Theile, Carsten. Übungsbuch IFRS. Wiesbaden: Gabler, 2010. http://dx.doi.org/10.1007/978-3-8349-8822-5.

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Brösel, Gerrit, and Christian Zwirner, eds. IFRS-Rechnungslegung. München: OLDENBOURG WISSENSCHAFTSVERLAG, 2009. http://dx.doi.org/10.1524/9783486848922.

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Williams, Cen. Rhys Ifans. Cardiff: Relay Publications, 2000.

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lemy, Frank Barthe. Handbuch IFRS. 2nd ed. Freiburg: Rudolf Haufe Verlag & Co. KG, 2005.

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Book chapters on the topic "Ifns"

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Schindler, Christian, and Li Song. "IFNS and STATs, an Incestuous Relationship." In Signal Transducers and Activators of Transcription (STATs), 137–54. Dordrecht: Springer Netherlands, 2003. http://dx.doi.org/10.1007/978-94-017-3000-6_10.

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Galani, Ioanna E., Ourania Koltsida, and Evangelos Andreakos. "Type III interferons (IFNs): Emerging Master Regulators of Immunity." In Advances in Experimental Medicine and Biology, 1–15. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-15774-0_1.

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Nagarajan, Uma M. "Induction and Function of Type I IFNs During Chlamydial Infection." In Bacterial Activation of Type I Interferons, 97–108. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-09498-4_9.

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Appleton, Kathryn M., Ian Cushman, Yuri K. Peterson, Balachandran Manavalan, Shaherin Basith, Sangdun Choi, Akihiro Kimura, et al. "IFNG." In Encyclopedia of Signaling Molecules, 891. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_100637.

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Baumunk, Henrik. "IFRS-Rechnungslegung." In Immobilienwirtschaftslehre - Management, 365–91. Wiesbaden: Springer Fachmedien Wiesbaden, 2017. http://dx.doi.org/10.1007/978-3-658-18193-2_14.

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Henkel, Knut. "IAS/IFRS." In Rechnungslegung von Treasury-Instrumenten nach IAS/IFRS und HGB, 100–246. Wiesbaden: Gabler, 2010. http://dx.doi.org/10.1007/978-3-8349-8806-5_3.

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Zielke, Carsten. "Grundzüge des IFRS: Phase II (IFRS 17)." In IFRS für Versicherer, 27–52. Wiesbaden: Springer Fachmedien Wiesbaden, 2018. http://dx.doi.org/10.1007/978-3-658-20734-2_8.

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Yatsuhashi, Hiroshi. "IFN Receptor and IFN Signals." In Therapy for Viral Hepatitis and Prevention of Hepatocellular Carcinoma, 176–85. Tokyo: Springer Japan, 2004. http://dx.doi.org/10.1007/978-4-431-53977-3_17.

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Zinser, Franz. "Rahmenkonzept der IFRS und Regelungen des IFRS 8." In Segmentberichterstattung nach IFRS 8, 57–88. Wiesbaden: Springer Fachmedien Wiesbaden, 2019. http://dx.doi.org/10.1007/978-3-658-28036-9_3.

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Belohuby, Richard. "Kundenwertcontrolling und IFRS." In Kundenwertcontrolling und IFRS Rechnungslegung, 153–209. Wiesbaden: Springer Fachmedien Wiesbaden, 2013. http://dx.doi.org/10.1007/978-3-658-03497-9_4.

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Conference papers on the topic "Ifns"

1

Zhang, Hengshan, Qinghua Zheng, Ting Liu, and Yu Qu. "Mixed Intuitionistic Fuzzy Aggregation Operators decreasing results of unusual IFNs." In 2016 IEEE International Conference on Fuzzy Systems (FUZZ-IEEE). IEEE, 2016. http://dx.doi.org/10.1109/fuzz-ieee.2016.7737783.

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Oke, V., I. Gunnarsson, J. Dorschner, A. Zickert, TB Niewold, and E. Svenungsson. "S5A:4 Circulating type i, ii and iii interferons (ifns) associate with ifn-scores, but define distinct subsets of active sle." In 11th European Lupus Meeting, Düsseldorf, Germany, 21–24 March 2018, Abstract presentations. Lupus Foundation of America, 2018. http://dx.doi.org/10.1136/lupus-2018-abstract.27.

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Carlsen, E., and H. Prydz. "ROLE OF BIOLOGICAL RESPONSE MODIFIERSIN THE REGULATION OF THROMBOPLASTIN SYNTHESIS IN MONOCYTES AND ENDOTHELIAL CELLS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643736.

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A rabbit polyclonal antibody which was monospecific for thromboplastin (TP) apoprotein from human brain according to a number of criteria was used to screen two human placenta cDNA libraries in the expression vector Agtll, one randomly primed and one oligo-dT primed, by the method of Young and Davis. 23 positive clones expressing TP related antigen were isolated and plaque purified. DNA from the different clones was isolated and the TPcDNA inserts released by EcoRl digestion. The inserts could be classified into11 size classes ranging from approx. 300-1100 base pairs.The largest insert (1100 bp) was subcloned intothe plasmid vector pGEM-1. When the nick-translated plasmid (pTP4-l) was used as a probe to screen the phage clones by slot blot hybridization all the 23clones hybridized to the 1100 bp insert. A XgtllTP4 lysogen expressed B-galactosidase- TP4 fusion peptide upon IPTG induction as shown by immunobinging studied using two different antibodies to TP apoprotein: the rabbit antibody originally used to screen the libraries and an antibody raised in goat against human brain TP purified by affinity chromatography on a Factor Vll-antiVII-agarose column.Cytokines mediate many of the cellular interactions in the inflammatory and immune response systems and have a variety of actions. We have investigated the effect of rIL-1a/$,rIL-2, rlFNa/y and rTNFa on thromboplastin synthesis (TPL) in monocytes (M) and human umbilical vein endothelial cells (HUVEC). Recombinant IL- 1a and IL-16 both induced a dose dependent increase in TPL activity of monocyte (8-fold) and HUVEC cultures (15-fold) at 6h. The increase levelled off at interleukinconcentrations of 50-100u/ml. Recombinant IL-2 at 50u/ml induced a 5-fold rise in monocytes TPL. The effect of rIL-2 on HUVEC TPL synthesis at 6 h was smaller than on monocytes but still clearly significant at dose dependent. Recombinant IFN-Y (10 -10 u/ml) increased.TPL activity in HUVEC at 6h and 16 h in adose dependent manner, whereas no effect of rIFN-Y and IFN-a (1-10 u/ml) on M TPL was seen. When LPS (5pg/ml) was used to induce TPL synthesis, additional stimulation with rIFN-Y further enhanced HUVEC TPL activity, but decreased M TPL activity. Recombinant IFNa also decreased LPS induced TPL synthesis in M andhad no effect on HUVEC TPL. Recombinant TNFa (0.3x104u/ml) increased HUVEC TPL 7-fold at 6h. There wasno effect on M TPL synthesis. No endotoxin was detected in any of these preparations. CONCLUSIONS: Some biological response modifiers induced thromboplastin synthesis in monocytes (IL-ia, IL-13, IL-2) and in human umbilical vein endothelial cells (IL-ia, IL-18, IL-2, TNFa and IFNY). Some had no direct effect on TPL synthesis but inhibited the response to monocytes to other thromboplastin-inducing agents like LPS (IFNa and IFNY).
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Fermaintt, Charles S., Shayne Hastings, Susan L. Mooberry, and April L. Risinger. "Abstract P5-05-03: Eribulin treatment activates type 1 IFNs to promote a gene expression signature associated with antitumor immunity." In Abstracts: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, Texas. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.sabcs19-p5-05-03.

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Loisel, Dagan A., Zheng Tan, Gaixin Du, Christopher Tisler, Kathy A. Roberg, Ronald E. Gangnon, Michael D. Evans, James E. Gern, Robert F. Lemanske, Jr, and Carole Ober. "IFNG Genotype And Sex Interact To Influence IFN-³ Response And Asthma Risk In Early Childhood." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1304.

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Abdelsalam Hussein, Yasmin Adel, and Yousra Sadeq. "THU0255 IMPACT OF IL34, IFNα AND IFN-λ1 ON DISEASE ACTIVITY OF SLE PATIENTS IN EGYPT." In Annual European Congress of Rheumatology, EULAR 2019, Madrid, 12–15 June 2019. BMJ Publishing Group Ltd and European League Against Rheumatism, 2019. http://dx.doi.org/10.1136/annrheumdis-2019-eular.1304.

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Tusan, Radoslav. "THE IMPACT OF THE ADOPTION OF INTERNATIONAL FINANCIAL REPORTING STANDARDS ON THE FINANCIAL SITUATION AND PERFORMANCE OF THE COMPANY." In Sixth International Scientific-Business Conference LIMEN Leadership, Innovation, Management and Economics: Integrated Politics of Research. Association of Economists and Managers of the Balkans, Belgrade, Serbia, 2020. http://dx.doi.org/10.31410/limen.s.p.2020.37.

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This paper deals with the evaluation of the impact of the adoption of International Financial Reporting Standards (IFRS) on the financial situation and performance of the company. The Slovak Accounting Act allows accounting and reporting under IFRS for two types of entities - explicitly specified by law (e.g. banks, insurance companies, stock exchange); and those that meet specified size criteria. The analyzed company met the size criteria and IFRS has been applying since 2018. The transition from Slovak accounting procedures to IFRS has an impact on the classification of individual items of assets and liabilities, their structure, and the classification of related costs and revenues. The transition to IFRS thus has an impact on the company's financial position and performance. The paper set out two objectives of the research: 1) the transition to IFRS caused an insignificant change in the company's financial indicators; 2) the transition to IFRS caused a significant change in the company's financial indicators. The results of the analysis show changes in the structure of the company's assets and liabilities, the amount of income and expenses, and the less significant impact of the adoption of IFRS on financial indicators.
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Кабанова, Алена Михайловна, and Людмила Ивановна Кругляк. "IFRS 9 «FINANCIAL INSTRUMENTS» IN THE CONTEXT OF SECURITY ECONOMIC SECURITY OF CREDIT INSTITUTIONS." In Национальная безопасность России: актуальные аспекты: сборник избранных статей Всероссийской научно-практической конференции (Санкт-Петербург, Январь 2021). Crossref, 2021. http://dx.doi.org/10.37539/nb189.2021.67.54.006.

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В статье рассматриваются актуальные особенности Между-народного стандарта финансовой отчетности (IFRS) 9 при их внедрении в российской банковской отчетности. Применение МФСО требует новых знаний, принципов и навыков специалистов соответствующих служб. МСФО - это не свод строгих, конкретных правил, а определенный набор требований и принципов. The article discusses the current features of the International Financial Reporting Standard (IFRS) 9 in the implementation and transformation of Russian banking reporting. The application of IFRS requires new knowledge, principles and skills of specialists of the relevant services. IFRS is not a set of strict, specific rules, but a specific set of requirements and principles.
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Silva, Camila L., João Augusto Felberg, João Cabano, and Anderson C. Lima. "Um Panorama sobre a Acessibilidade para Transparência em Sites de Institutos Federais do Centro-Oeste do Brasil." In V Workshop de Transparência em Sistemas. Sociedade Brasileira de Computação - SBC, 2017. http://dx.doi.org/10.5753/wtrans.2017.3122.

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Este trabalho tem por objetivo verificar o grau de acessibilidade em websites dos Institutos Federais (IF's) da região centro-oeste do Brasil. Os IF's são instituições públicas de excelência no ensino técnico e superior no páıs. A cada ano milhares de candidatos e alunos buscam informações e serviços nos websites dos IF's. Este é um público vasto e que possivelmente também é composto por pessoas com algum grau de deficiência. Verificar se os websites de instituições de ensino são acessíveis é uma tarefa imprescindível, pois se for o caso, é possível sugerir a inserção de recomendações de acessibilidade, que são pré-requisitos para um acesso transparente e universal da informação.
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Dwiyani, Fitri, and Amal C. Sjaaf. "Analysis of Pharmaceutical Installations Management at Kambang Hospital, Jambi." In The 7th International Conference on Public Health 2020. Masters Program in Public Health, Universitas Sebelas Maret, 2020. http://dx.doi.org/10.26911/the7thicph.04.20.

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ABSTRACT Background: Hospital Pharmacy Installation (IFRS) was one of 5 revenue centres as well as being the primary support for the hospital which has full authority in managing various pharmaceutical preparations. Therefore, pharmaceutical supplies require careful and precise management through a one-door system. This study aimed to determine the management system and identify the various problems that exist in the pharmacy installation at Kambang Jambi Hospital. Subjects and Method: This study was a qualitative study conducted on IFRS at Kambang Jambi Hospital from August to September 2020. The data were obtained from primary data in the form of in-depth interviews with stakeholders related to IFRS and field observations, as well as secondary data in the form of document review. The data were collected by in-depth interview guide. The data was reported by 5 Whys Analysis diagram. Results: Based on field observations at IFRS Kambang Jambi Hospital, it was found that there were still many problems at almost every stage of pharmaceutical supply management starting from planning, procurement, receiving, storage, distribution, control, deletion, recording and reporting, as well as monitoring and evaluation. When the problem is identified more deeply using 5 Whys Analysis, the roots of these various problems are obtained, namely: 1) There has not been an adequate Pharmacy and Therapy Committee (KFT) in the management of the pharmaceutical installation at Kambang Jambi Hospital, 2) The majority of KFT members have assumed structural positions at Kambang Jambi Hospital so that it does not focus on KFT duties, 3) KFT does not regularly hold monthly meetings and evaluations, 4) The ineffective role of SPI at Kambang Jambi Hospital in monitoring and evaluating IFRS performance, 5) SIMRS still depends on outsiders not always standby at the hospital when there are problems. Conclusion: Re-organized the pharmacy and therapy committee to carry out a continuous review of the hospital formularies to be more effective and minimize medication errors. Keywords: IFRS, IFRS management, drug procurement, KFT. Correspondence: Fitri Dwiyani. Postgraduate Student for Hospital Administration Studies, Faculty of Public Health, University of Indonesia, Depok City, West Java. Email: fitridwiyani14@gmail.com. Mobile: 081221005831/081221005831 DOI: https://doi.org/10.26911/the7thicph.04.20
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Reports on the topic "Ifns"

1

IFNA, IFNA. IFNA virtual regional meeting. Washington, DC: International Food Policy Research Institute, 2020. http://dx.doi.org/10.2499/p15738coll2.133995.

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Dilnot, Andrew, Helen Simpson, and Carl Emmerson. IFS Green Budget 2002. Institute for Fiscal Studies, January 2002. http://dx.doi.org/10.1920/co.ifs.2002.0087.

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Johnson, Paul, Helen Miller, and Carl Emmerson. IFS Green Budget 2014. Institute for Fiscal Studies, February 2014. http://dx.doi.org/10.1920/re.ifs.2014.0091.

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Johnson, Paul, Carl Emmerson, and Robert Joyce. IFS Green Budget 2015. Institute for Fiscal Studies, February 2015. http://dx.doi.org/10.1920/re.ifs.2014.0106.

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Johnson, Paul, Robert Joyce, and Carl Emmerson. IFS Green Budget 2016. Institute for Fiscal Studies, February 2016. http://dx.doi.org/10.1920/re.ifs.2016.0112.

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Emmerson, Carl, Robert Joyce, and Paul Johnson. IFS Green Budget 2017. The IFS, February 2017. http://dx.doi.org/10.1920/re.ifs.2017.0124.

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Zaranko, Ben, Tom Waters, Isabel Stockton, Christian Schulz, Benjamin Nabarro, David Miles, Alex Davenport, et al. IFS Green Budget 2020. The IFS, October 2020. http://dx.doi.org/10.1920/re.ifs.2020.0180.

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Johnson, Paul, Christine Farquharson, and Carl Emmerson. IFS Green Budget 2019. The IFS, October 2019. http://dx.doi.org/10.1920/re.ifs.2019.0163.

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Chote, Robert, Helen Simpson, and Carl Emmerson. The IFS Green Budget 2003. IFS, January 2003. http://dx.doi.org/10.1920/co.ifs.2003.0092.

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Oldfield, Zoe, Robert Chote, Carl Emmerson, and David Miles. The IFS Green Budget 2005. IFS, January 2005. http://dx.doi.org/10.1920/co.ifs.2005.0097.

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