Academic literature on the topic 'Interferony (IFNy)'
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Journal articles on the topic "Interferony (IFNy)"
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Edwards, Kimberlee, Kristen M. Braun, Glenn Evans, Amod O. Sureka, and Samuel Fan. "Mainstream and sidestream cigarette smoke condensates suppress macrophage responsiveness to interferony." Human & Experimental Toxicology 18, no. 4 (April 1999): 233–40. http://dx.doi.org/10.1191/096032799678839978.
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Sidestream smoke evolves from the smoldering end of a cigarette while the smoker is not puffing, and contributes substantially to environmental tobacco smoke (ETS). In contrast, main stream smoke emerges from the butt end of the cigarette and is mainly inhaled by the smoker. This study was performed to compare the effects of short-term exposure to cigarette smoke condensates prepared from sidestream (CSCSS) and mainstream cigarette smoke (CSC-MS) on macrophage basal metabolism and responsiveness to two different stimuli, bacterial lipopolysaccharide (LPS) and interferony (IFNy). Despite their generation at different temperatures and their different chemical composition, CSC-SS and CSC-MS had similar effects on macrophages. Both enhanced macrophage basal metabolism and responsiveness to LPS. Macrophage responsiveness to IFNy, assessed by their expression of four functional capacities, was suppressed by both CSC-SS and CSC-MS. The four assessed IFNy-inducible functional capacities were: enhanced phagocytosis of immuoglobulin-opsonized sheep red blood cells, TPAinduced peroxide production, class II major histocompatibility complex expression, and nitric oxide synthesis with LPS co-stimulation. The effects of CSCSS and CSC-MS were similar qualitatively; they differ quantitatively in some cases, with CSC-MS generally effective at lower concentrations (expressed as cigarette-equivalents) than CSCSS. Considering dilution of sidestream smoke in room air and loss during passage through the respiratory system, we expect to deliver the maximal dose to lung macrophages in situ only in rooms dense with smokers. However, only a fraction ofthe maximal dose can partially suppress induction of some fiuctions, such as nitric oxide production and MHC expression. Macrophages play critical roles in tissue modeling during development. Of particular concern are neonates, whose organs are still undergoing growth and development, and are therefore susceptible to impaired development. If involuntary exposure to ETS hinders induction of macrophage functional capacities by cytokines, then development of the lungs and perhaps other organs would be impaired. In general, since macrophages are potent effectors and regulators of immunity, impairment of their responsiveness to cytokine must disrupt the proper functioning of the immune system.
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Coldbeck-Shackley, Rosa C., Ornella Romeo, Sarah Rosli, Linden J. Gearing, Jodee A. Gould, San S. Lim, Kylie H. Van der Hoek, et al. "Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection." PLOS Pathogens 19, no. 3 (March 10, 2023): e1010843. http://dx.doi.org/10.1371/journal.ppat.1010843.
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The immunological surveillance factors controlling vulnerability of the female reproductive tract (FRT) to sexually transmitted viral infections are not well understood. Interferon-epsilon (IFNɛ) is a distinct, immunoregulatory type-I IFN that is constitutively expressed by FRT epithelium and is not induced by pathogens like other antiviral IFNs α, β and λ. We show the necessity of IFNɛ for Zika Virus (ZIKV) protection by: increased susceptibility of IFNɛ-/- mice; their “rescue” by intravaginal recombinant IFNɛ treatment and blockade of protective endogenous IFNɛ by neutralising antibody. Complementary studies in human FRT cell lines showed IFNɛ had potent anti-ZIKV activity, associated with transcriptome responses similar to IFNλ but lacking the proinflammatory gene signature of IFNα. IFNɛ activated STAT1/2 pathways similar to IFNα and λ that were inhibited by ZIKV-encoded non-structural (NS) proteins, but not if IFNε exposure preceded infection. This scenario is provided by the constitutive expression of endogenous IFNε. However, the IFNɛ expression was not inhibited by ZIKV NS proteins despite their ability to antagonise the expression of IFNβ or λ. Thus, the constitutive expression of IFNɛ provides cellular resistance to viral strategies of antagonism and maximises the antiviral activity of the FRT. These results show that the unique spatiotemporal properties of IFNε provides an innate immune surveillance network in the FRT that is a significant barrier to viral infection with important implications for prevention and therapy.
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Liu, Bi-Sheng, Harry L. A. Janssen, and André Boonstra. "IL-29 and IFNα differ in their ability to modulate IL-12 production by TLR-activated human macrophages and exhibit differential regulation of the IFNγ receptor expression." Blood 117, no. 8 (February 24, 2011): 2385–95. http://dx.doi.org/10.1182/blood-2010-07-298976.
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Abstract The interferon-λ (IFNλ) family of cytokines, consisting of interleukin-28A (IFNλ2), IL-28B (IFNλ3), and IL-29 (IFNλ1), have been extensively studied for their antiviral activities. However, little is known about the effect of IFNλ on antigen-presenting cells. In the present study, we show for the first time that IL-29 can increase Toll-like receptor (TLR)–induced IL-12p40 production by human monocyte-derived macrophages. In contrast, IL-29 did not affect monocytes or monocyte-derived dendritic cells (DCs) because of restricted IL-28 receptor α chain expression by macrophages. Furthermore, IL-29–treated macrophages were more responsive to IFNγ, because IL-29 enhanced IFNγ-induced IL-12p40 and tumor necrosis factor (TNF) production by macrophages on R848 stimulation. However, IFNα suppressed IFNγ-induced IL-12p40 and tumor necrosis factor TNF production by human macrophages. The differential effects of IL-29 and IFNα on the responsiveness of macrophages to IFNγ could not be explained by an effect on TLR7 or TLR8 mRNA expression or by altered IL-10 signaling. However, we demonstrated that IL-29 up-regulated, whereas IFNα down-regulated, the surface expression of the IFNγ receptor 1 chain on macrophages, thereby resulting in differential responsiveness of TLR-challenged macrophages to IFNγ. Our findings on the differences between IFNα and IL-29 in modulating TLR-induced cytokine production by macrophages may contribute to understanding the role of IFNs in regulating immunity to pathogens.
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Lortat-Jacob, H. "Interferon and heparan sulphate." Biochemical Society Transactions 34, no. 3 (May 22, 2006): 461–64. http://dx.doi.org/10.1042/bst0340461.
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In 1954, substances that protected cells from viral infection were discovered and named IFN (interferon). This family of cytokines, which were the first to be used in clinical therapy, is classified into type I and II IFNs. Type I mainly consists of IFNα and IFNβ subtypes, which are structurally related and bind to a common receptor. IFNγ, the sole type II IFN, is structurally unrelated, binds to a different receptor and, as a dimer, strongly interacts with HS (heparan sulphate). In addition to its antiviral activity, it modulates nearly all phases of immune and inflammatory responses. IFNγ binding to HS controls the blood clearance, the subsequent tissue targeting and the local accumulation of the cytokine. It also regulates IFNγ activity by a unique mechanism involving a controlled processing of the C-terminal peptide. The binding site encompasses an N-acetylated glucosamine-rich domain separating two highly sulphated sequences that each binds to one IFNγ monomer. Based on this template, a set of glycoconjugate mimetics that would mimic the IFNγ binding site has been synthesized. One of these molecules displays high affinity for the cytokine and inhibits binding to both HS and IFNγR (IFNγ receptor), the cell-surface receptor. These results validate the HS structural determinants for IFNγ recognition, and provide a new strategy to inhibit IFNγ in a number of diseases in which the cytokine has been identified as a target.
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Hamilton, Jennie A., Qi Wu, PingAr Yang, Bao Luo, Shanrun Liu, Jun Li, Huixian Hong, et al. "Single cell analysis revealed distinct B-cell subpopulations that produce or respond to type I interferon in SLE." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 40.12. http://dx.doi.org/10.4049/jimmunol.200.supp.40.12.
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Abstract We previously showed that B-cell endogenous expression of interferon beta (IFNβ) is associated with the development of autoreactive B cells in BXD2 autoimmune mice. As among all type I IFNs, IFNβ exhibits the highest affinity to IFNAR1 and IFNAR2 and IFNβ also can stimulate IFNαs, there is a pressing need for a better understanding of the source and responses of IFNβ in systemic lupus erythematosus (SLE). Flow cytometry and super-resolution imaging analysis showed increased expression of IFNβ in B cells obtained from PBMCs of SLE patients compared to healthy controls. The importance of SLE B-cell endogenous IFNβ in regulating TLR7-mediated responses was identified when CL264 (a TLR7 ligand) plus anti-Ig-induced CD69 and survival of purified B cells were significantly and equivalently suppressed by an anti-IFNβ or an anti-IFNAR1 blocking antibody. We next carried out single cell qRT-PCR analysis to determine if B-cell endogenous IFNβ acts in an autocrine or paracrine manner to modulate IFN stimulated genes (ISGs). Hierarchical analysis revealed three prominent and consistent clusters, consisting of an IFNB+ cluster, an ISG+ cluster, and an IFNA+ cluster in naïve B cells isolated from 3 SLE patients. Cells within the IFNB+ cluster expressed higher levels of IFNB, IFNA1, IFNA8, and TLR7. Cells within the ISG+ cluster expressed higher levels of IFNAR1, IFNAR2, BAFFR, MX1, RIG1 and TLR9. Cells within the IFNA+ cluster expressed higher levels of IFNA4, IFNA10, IFNA14, IFNA16, IFNA17, and TLR3. Together, the results reveal (1) B cells as an important source of IFNβ in modulating TLR7 responses in SLE; (2) a well-orchestrated program in modulating IFNβ donor versus responder B cells; and (3) some patients may benefit from specific targeting of IFNβ.
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Pizutelli, Vanessa, Carley Tasker, Lishan Sue, Wuyuan Lu, and Theresa Chang. "Human IFNe and IFNa modulate immune and anti-HIV functions through the differential involvement of IFNa receptors." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 66.5. http://dx.doi.org/10.4049/jimmunol.202.supp.66.5.
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Abstract Interferon e (IFNe) is a critical innate immune mediator that protects the host against sexually transmitted infections. Although the current paradigm is that IFNɛ is a type I IFN and signals through IFNa receptors (IFNARs), our and other published results show that IFNɛ has unique gene regulatory and immune functions that are distinct from IFNa. IFNɛ is constitutively expressed in the mucosa, and highly abundant in the female reproductive tract. It exhibits superior mucosal immune activity compared to IFNa/b. We have previously shown that that human IFNe induces an anti-HIV state through a mechanism independent of known type I IFN-induced HIV host restriction factors in primary macrophages. IFNɛ induces phagocytosis and reactive oxygen species that contribute to anti-HIV activity. In this study, we determined the involvement of IFNARs in immune modulation and HIV inhibition by human IFNɛ in comparison to human IFNa. Human IFNɛ elicited a more robust immune response than human IFNa2 in PBMCs and primary macrophages. The immune profiles in response to human IFNɛ were cell-type dependent. Antibodies (Abs) against IFNAR1 or IFNAR2 blocked induction of interferon-stimulated genes (ISGs) by human IFNa2 and murine IFNe. However, anti-IFNAR2 but not anti-IFNAR1 Ab blocked human IFNe-mediated ISG induction. Interestingly, anti-IFNAR1 or anti-IFNAR2 Ab blocked cytokine induction by human IFNa2 but not by human IFNe. Finally, we found that both IFNAR1 and IFNAR2 were involved in anti-HIV activity of human IFNa2 but only IFNAR2 was involved in HIV inhibition by human IFNe. In summary, our results indicate that human IFNe, not a conventional type I IFN, modulates immune and anti-HIV functions through distinct mechanisms from IFNa2.
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Chang, Theresa Li-Yun, Carley Tasker, Selvakumar Subbian, Pan Gao, Jennifer Couret, Carly Levin, Saleena Ghanny, et al. "Interferon epsilon protects primary macrophages against HIV infection." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 158.15. http://dx.doi.org/10.4049/jimmunol.198.supp.158.15.
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Abstract Interferon epsilon (IFNe) is a unique type I IFN that is not induced by pattern-recognition response elements. IFNɛ is constitutively expressed in mucosal tissues including the female genital mucosa. Although the direct anti-viral activity of IFNe was thought to be weak compared to IFNa, IFNe controls Chlamydia muridarum and herpes simplex virus 2 in mice, possibly through modulation of immune response. We show here that IFNe induces an antiviral state in human macrophages that blocks HIV-1 replication. IFNe had little or no protective effect in activated CD4+ T cells or transformed cell lines unless activated CD4+ T cells were infected with replication competent HIV-1 at a low MOI. The block to HIV infection of macrophages was maximal after 24 h of treatment and was reversible. IFNe acted on early stages of the HIV life cycle including viral entry, reverse transcription and nuclear import. The protection did not appear to operate through known type I IFN-induced HIV host restriction factors such as APOBEC3A and SAMHD1. IFNe-stimulated immune mediators and pathways had the signature of type I IFNs but were distinct from IFNα2. IFNe induced significant phagocytosis and reactive oxygen species, which contributed to the block to HIV replication in macrophages. These findings indicate that IFNe induces an antiviral state in macrophages that is mediated by different factors than those induced by IFNa2. Understanding the mechanism of IFNe-mediated HIV inhibition through immune modulation has implications for prevention.
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Li, Yuanyuan, Yueqi Song, Leqing Zhu, Xiao Wang, Brittany Richers, Donald Y. M. Leung, and Lianghua Bin. "Interferon Kappa Is Important for Keratinocyte Host Defense against Herpes Simplex Virus-1." Journal of Immunology Research 2020 (January 3, 2020): 1–8. http://dx.doi.org/10.1155/2020/5084682.
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Type I interferon kappa (IFNκ) is selectively expressed in human keratinocytes. Herpes simplex virus-1 (HSV-1) is a human pathogen that infects keratinocytes and causes lytic skin lesions. Whether IFNκ plays a role in keratinocyte host defense against HSV-1 has not been investigated. In this study, we found that IFNκ mRNA expression was induced by addition of recombinant IFNκ and poly (I:C); and its expression level was significantly greater than IFNa2, IFNb1, and IFNL1 in both undifferentiated and differentiated normal human epidermal keratinocytes (NHEKs) under resting and stimulation conditions. Although IFNe was expressed at a relatively higher level than other IFNs in resting undifferentiated NHEK, its expression level did not change after stimulation with recombinant IFNκ and poly (I:C). HSV-1 infection inhibited gene expression of IFNκ and IFNe in NHEK. Silencing IFNκ in NHEK led to significantly enhanced HSV-1 replication in both undifferentiated and differentiated NHEK compared to scrambled siRNA-transfected cells, while the addition of recombinant IFNκ significantly reduced HSV-1 replication in NHEK. In addition, we found that IFNκ did not regulate protein expression of NHEK differentiation markers. Our results demonstrate that IFNκ is the dominant type of IFNs in keratinocytes and it has an important function for keratinocytes to combat HSV-1 infection.
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Nguyen, Benjamin H., Elizabeth Troisi, and Diane E. Griffin. "Interferon Regulatory Factor 7-mediated induction of interferon-α is required for survival from alphavirus encephalomyelitis." Journal of Immunology 210, no. 1_Supplement (May 1, 2023): 75.35. http://dx.doi.org/10.4049/jimmunol.210.supp.75.35.
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Abstract Alphaviruses are a group of arthropod-borne viruses that have the capacity to cause encephalomyelitis, which is inflammation of the brain and spinal cord due to the immune response to viral infection, and can result in fever, headache, and neurologic disease such as cognitive impairment, seizures, ataxia, and paralysis. Neurons are the primary target cells of Sindbis virus (SINV), the prototypic alphavirus; however, due to the indispensable nature of neurons, mechanisms of viral clearance from the central nervous system (CNS) during recovery cannot depend on immune-mediated killing of infected neurons and is therefore specialized. We have previously shown that interferon (IFN) regulatory factor (IRF) 7, a transcription factor important for amplification of type I IFN (mainly IFNα), is required for survival from infection with SINV. Mice deficient in IRF7 succumb to infection – despite local production of IFNβ – while wild type (WT) mice recover. Treatment of Irf7−/−mice with IFNα rescues the WT phenotype, suggesting that IRF7-mediated induction of IFNα and subsequent downstream signaling is required for survival from SINV infection. Additionally, Ifnb−/−mice do not phenocopy Irf7−/−mice, further suggesting that IFNα is required for survival while IFNβ is dispensable despite usage of the same receptor. Interestingly, Ifnb−/−mice have similar viral titers to Irf7−/−mice, implying that the protective effects of IFNα are independent from restriction of viral replication. These findings show subtype-specific differences in protection by type I IFN and can inform treatment options for alphavirus-induced encephalomyelitis. These works have been funded by the U.S. National Institutes of Health (R01 NS087539 and T32 AI007417).
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Chen, Bohan, Chandan Gurung, Jason Guo, Chulan Kwon, and Yan-Lin Guo. "Pluripotent stem cells are insensitive to the cytotoxicity of TNFα and IFNγ." Reproduction 160, no. 4 (October 2020): 547–60. http://dx.doi.org/10.1530/rep-20-0215.
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Recent studies have demonstrated that embryonic stem cells (ESCs) have an underdeveloped innate immune system, but the biological implications of this finding are poorly understood. In this study, we compared the responses of mouse ESCs (mESCs) and mESC differentiated fibroblasts (mESC-FBs) to tumor necrosis factor α (TNFα) and interferons (IFNs). Our data revealed that TNFα, IFNα, IFNβ, or IFNγ alone do not cause apparent effects on mESCs and mESC-FBs, but the combination of TNFα and IFNγ (TNFα/IFNγ) showed toxicity to mESC-FBs as indicated by cell cycle inhibition and reduced cell viability, correlating with the expression of inducible nitric oxide synthase (iNOS). However, none of these effects were observed in mESCs that were treated with TNFα/IFNγ. Furthermore, mESC-FBs, but not mESCs, are vulnerable to cytotoxicity resulting from lipopolysaccharide (LPS)-activated macrophages. The insensitivity of mESCs to cytotoxicity in all cases is correlated with their lack of responses to TNFα and IFNγ. Similar to mESCs, human ESCs (hESCs) and iPSCs (hiPSCs) do not respond to TNFα and are not susceptible to the cytotoxicity of TNFα, IFNβ, or IFNγ alone or in combination that significantly affects human foreskin fibroblast (hFBs) and Hela cells. However, unlike mESCs, hESCs and hiPSCs can respond to IFNγ, but this does not cause significant cytotoxicity in hESCs and hiPSCs. Our findings in both mouse and human PSCs together support the hypothesis that attenuated innate immune responses could be a protective mechanism that limits immunologic cytotoxicity resulting from inflammatory and immune responses.
Dissertations / Theses on the topic "Interferony (IFNy)"
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Chen, Shu. "Studies on interferon (IFN) induction and isolation of IFN-inducing mutant viruses." Thesis, University of St Andrews, 2011. http://hdl.handle.net/10023/1678.
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The interferon (IFN) system is a powerful antiviral defense system. Host cell pattern recognition receptors (PRRs) recognise pathogen-associated molecule patterns (PAMPs) which when activated, lead to the transcription of the IFN-β gene. As a consequence IFN is secreted from the cell and activates the JAK-STAT pathway to up-regulate the transcription of IFN-stimulated genes (ISGs). The products of many ISGs inhibit viral replication and cell proliferation. Viruses encode IFN antagonists that dampen down the IFN response, making it less effective. However, within a virus population, there are always likely to be naturally occurring mutant viruses that have lost the ability to circumvent the host IFN response, and if isolated, these viruses would be unlikely to cause severe disease in the host and may therefore be developed as live attenuated virus vaccine candidates. To develop a methodology to rapidly isolate IFN-inducing mutant viruses, we generated an A549 reporter cell-line in which expression of GFP was driven by the IFN-β promoter. Using this cell-line, we show that the number of cells that became positive for GFP correlated with the amount of IFN secreted by the infected cells and the number of defective interfering (DI) particles within the virus preparations. However, we were unable to isolate IFN-inducing mutant viruses using the A549/pr(IFN-β).GFP cell-line(s). Possible reasons for this may be either that, in cells infected by IFN-inducing mutant viruses, an antiviral state was established independent of IFN that prevented virus replication in the reporter cells in which the IFN-β promoter was activated; or the viruses that activated the IFN-β promoter were DIs only which were not be able to replicate without non-defective helper viruses. A549/pr(IFN-β).GFP cells are also being used for high throughput assays to screen chemical libraries for compounds that block IFN induction. Such compounds may be potential candidates for anti-inflammatory drugs.
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Walker, Angela Marie Roberts R. M. "The type I IFN of Bos taurus." Diss., Columbia, Mo. : University of Missouri-Columbia, 2008. http://hdl.handle.net/10355/6864.
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The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on April 1, 2010). Vita. Thesis advisor: R. Michaels Roberts. "May 2008" Includes bibliographical references
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Prando, Carolina Cardoso de Mello. "O papel crucial do eixo IL 12/23-IFNy para o desenvolvimento e ativação do sistema NADPH oxidase humano." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308286.
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Orientador: Antonio Condino NetoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: O sistema NADPH oxidase fagocítico humano possui um papel importante na defesa contra microorganismos intracelulares, incluindo micobactérias. Mutações nas subunidades deste sistema resultam na Doença Granulomatosa Crônica (DGC). O gene CYBB, localizado no cromossomo X, codifica a subunidade gp91phox, e mutações neste gene são responsáveis por cerca de 60% dos casos de DGC. Cerca de 40 anos depois da identificação de DGC, foi identificado o primeiro dos 13 defeitos genéticos associados à Susceptibilidade Mendeliana à Micobacteriose, participantes do eixo IL12/23-IFN-?. Baseado no fato de que ambas as doenças predispõem a infecções por micobactérias e que o IFN-? is é um importante ativador do gene CYBB os autores se propuseram a estudar as características clinicas de pacientes latino-americanos com DGC e o sistema NADPH oxidase e expressão do gene CYBB em pacientes com defeitos no eixo IL-12/23-IFN-?. Em relação às características clínicas: história familiar de infecções graves e/ou de repetição, bem como reação adversa à vacina BCG, linfadenopatia, abscessos de pele e profundos estavam associados à DGC, em comparação com não-DGC avaliados pelo laboratório. Defeitos nos receptores IFNGR1 e IFNGR2 e cadeia B1 do receptor de IL-12 podem apresentar expressão do gene CYBB e atividade do sistema NADPH oxidas e diminuída ou abolida, chegando a níveis comparáveis a um paciente com DGC. O IFN- ? e seus receptores são essenciais para o desenvolvimento e ativação do sistema NADPH oxidase, e pacientes com comprometimento da função deste sistema devem também ser avaliados para defeitos do eixo IL12/23-IFN-? afetando secundariamente o sistema NADPH oxidase.
Abstract: The NADPH phagocytic oxidase system plays a crucial role in host defense against intracellular microorganisms, including mycobacteria. Mutations affecting subunits of this system result in Chronic Granulomatous Disease (CGD). The CYEE gene, located in the X chromosome, encodes gp91 phox, and mutations on this gene account for more than 60% of CGD cases. Almost 40 years after, the first of 13 different genetic disorders associated with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), was identified. The genes responsible for MSMD are part of the IL12/23-IFN-? axis. Based on the fact that both the diseases predispose to mycobacterial infections and that IFN-? is an important activator of CYBB gene, the authors aimed to describe clinical aspects of Latin American CGD patients and investigate ifthe NADPH oxidase system function and gp91phox expression would be affected in patients with defects in the IL-12/23-IFN-? axis. Regarding clinical features familial history of recurrent and sever infections, as well as adverse reactions to BCG vaccine, lymphadenopathy, skin and profound abscess were associated to DGC when compared to clinical features of non-CGD evaluated in the laboratory. Defects of IFNGR1 and IFNGR2 and IL12RB1 may present diminish.ed or abolished gene expression of CYBB and activity of NADPH oxidase system ate levels of a CGD patient. Based on that, we can conclude that IFN- ? and its receptor are essential for development and activation 9f NADPH oxidase system. In addition, patients who present an impaired superoxide release and/or failure on expressing gp91phox should also be evaluated for IL12/23-IFN-? axis affecting secondarily the NADPH oxidase system.
Doutorado
Doutor em Farmacologia
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Silva, Cláudia Maria de Melo. "Polimorfismos genéticos e associação com a produção de Interferon gama (IFN-y) em pacientes com Tuberculose pulmonar." Universidade Federal do Amazonas, 2014. http://tede.ufam.edu.br/handle/tede/2580.
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Previous issue date: 2014-04-28FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas
Tuberculosis (TB) is a chronic infection caused by Mycobacterium tuberculosis complex and remains a major worldwide public health problem, leading to almost 1.45 million deaths annually. The state of Amazonas has a high rate incidence of TB, about 68.3/100,000 inhabitants in 2012. Only 5 to 10% of infected individuals develop active TB. It has been suggested that host factors determine the immune response to pathogen. Thus, many immunogenetic researches have demonstrated TB associated genes, but in the north region, research in this field is still rare. This fact motivated the investigation of polymorphisms for IFNG, IL12B, CD80 and CD86 genes, which codify proteins for cellular immune response. Furthermore, IFN- concentration and its relation with genotypes found have been verified. A total of 177 patients and 224 controls (159 contacts and 65 non-contacts) were included in this study and DNA sequencing was performed for genes IFNG (SNP +874A/T and microsatellite +875), IL12B (SNPs +1030C/T, +1188A/C and +1254T/G), CD80 (SNPs -454 C/A, -387 T/C, -232 G/A, -79 C/G, -7T/C, +5C/A and an indel polymorphism -557_-561insCATGA) and CD86 (SNPs +1057G/A and +1079G/A). The IFN-y concentration was determined by enzyme-linked immunoassay. At IFNG, the presence of the allele +874A and the allele with 15 CA repeats were associated with susceptibility to pulmonary TB, while the allele +874T and the allele with 12 CA repeats were associated with protection from pulmonary TB. In addition, an association between genotype CC (SNP +1188A/C at IL12B) and increased risk of pulmonary TB was found. Furthermore, a significant difference between IFN- concentration and genotypes of SNP +1188A/C at IL12B and microsatellite at IFNG was observed, with decrease of IFN-at genotype CC and 15 CA repeats respectively. These outcomes lead to a better understanding of the immune response regulation for TB and help to determine the genetic profile of the Amazon population. Future researches are still needed for a better understanding of the role of other genes involved in the immune response to M. tuberculosis and their influence at the production of citokines like IFN-.
A Tuberculose (TB) é uma infecção crônica causada pelo complexo Mycobacterium tuberculosis sendo um importante problema de saúde pública mundial, levando a aproximadamente 1,45 milhões de mortes a cada ano. O estado do Amazonas possui uma alta incidência desta doença, atingindo 68,3 casos por 100 mil habitantes em 2012. Dos indivíduos infectados pelo bacilo, cerca de 5 a 10% desenvolvem a Tuberculose ativa, sugerindo que há fatores associados ao hospedeiro que determinam o destino da resposta imune ao patógeno. Neste contexto, diversos estudos em imunogenética têm demonstrado genes associados à TB, mas na região norte ainda são raras as pesquisas nesta área, fato que motivou a investigação da frequência dos polimorfismos nos genes IFNG, IL12B, CD80 e CD86, que codificam para proteínas fundamentais na resposta imune celular. Além disso, foi verificado se a concentração de IFN- está relacionada com o genótipo encontrado. Foram incluídas amostras de 177 pacientes e 224 controles (159 contatos e 65 não contatos) e realizado sequenciamento de DNA para os genes IFNG (SNP +874A/T e microssatélite +875), IL12B (SNPs +1030C/T, +1188A/C e +1254T/G), CD80 (SNPs -454 C/A, 454 C/A, 454 C/A, 454 C/A, -387 T/C, 387 T/C, 387 T/C, -232 G/A, 232 G/A, 232 G/A, -79 C/G, 79 C/G, 79 C/G, -7T/C e 7T/C e 7T/C e 7T/C e +5C/A+5C/A +5C/A e um polimorfismo indel -557_-561insCATGA) e CD86 (SNPs +1057G/A e +1079G/A). A determinação das concentrações de IFN-foi realizada através de ensaio imunoenzimático. Foi verificada uma associação do gene IFNG, entre a presença do alelo +874A e 15 repetições CA, como fator de risco para TB pulmonar assim como a presença do alelo +874T e 12 repetições CA como fatores de proteção contra TB pulmonar. Também foi encontrada uma associação do genótipo CC, do SNP +1188A/C no gene IL12B, como fator de risco ao desenvolvimento da TB pulmonar. Houve diferença significativa na concentração de IFN-entre os genótipos do SNP +1188A/C no gene IL12B e o microssatélite no gene IFNG, com menor produção no genótipo CC e 15 repetições CA respectivamente. Estes resultados contribuem para o melhor entendimento da regulação na resposta imune à TB e auxilia na determinação do perfil genético da população da região Amazônica. Estudos futuros são necessários para uma melhor compreensão do papel de outros genes envolvidos na resposta imunológica a M. tuberculosis e influência nos níveis de produção de citocinas como IFN-.
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Esteve-Solé, Ana. "Primary and secondary immunodeficiencies of the IL-12/IFN-γ axis." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/663924.
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IL-12/IFN-γ axis is a principal pathway for intramacrophagic pathogens immunity such as leishmania or mycobacteria. Alterations in this axis, being both congenic (causing the primary immunodeficiency Mendelian Susceptibility to Mycobacterial Disease, MSMD) or acquired (treatment with anti-TNF-α drugs) cause susceptibility to this type of microbes. MSMD causes susceptibility mainly to non-pathogenic mycobacteria, salmonella and candida; besides, MSMD- causing mutations have been detected in Mycobacterium tuberculosis and Leishmania patients. On the other hand, the death of an anti-TNF-α in-utero exposed infant after BCG vaccination together with the effect of anti-TNF-α drugs in tuberculosis reactivation in adults and the known tole of TNF-α in B cell maturation reveal the need for an in-depth study of in-utero exposition to anti-TNF-α drugs. With that our hypothesis is that patients with extrapulmonary Mycobacterium tuberculosis infection or visceral leishmaniasis have a primary dysfunction of the IL-12/IFN-γ axis and that exposure to anti-TNF-α antibodies during whole pregnancy in children born to mothers with inflammatory bowel disease affects the normal development of the neonatal immune system, conferring a secondary immunodeficiency, which includes a dysfunction of the IL- 12/IFN-γ axis.
Both extrapulmonary tuberculosis (n=23) and visceral leishmaniasis (n=24) patients presented alterations in the IL-12/IFN-γ pathway; however, we did not detect any complete defect. Concretely, the patients with extrapulmonary tuberculosis had a diminished response to IFN-γ while visceral leishmaniasis patients had a diminished production of IFN-g. Genetic study of these patients to unravel mutations causing partial forms of susceptibility to intramacrophagic infections is then needed. Besides, we detected an IL-12Rβ1 defect in a Peruvian patient that was misdiagnosed as multi-resistant tuberculosis, being a disseminated infection by the vaccine strain BCG. After the detection of the genetic defect, the patient was transferred to the National Institute of Health in the USA, where she received the appropriate treatment and the microbiological diagnosis was corrected resulting in the resolution of the infection. This case remarks the fact that suspicion of this forms of immune deficiency and their detection changes the prognostics and outcome of the patient.
The study of the effect of anti-TNF-α on the exposed infant immune system (n=7) revealed a T and B cell maturation defect that was corrected at 12 months, normal cell proliferation after mitogen stimulation and normal immunoglobulin production and vaccine response without an increase of severe infections. On the other hand, Treg cell frequency was low in exposed infants, without reaching normalization at 12 months of age. Treg cell frequency in neonates inversely correlated with anti-TNF-α through level in the mother during third trimester of pregnancy and with T cell proliferation after a mild mitogen stimulation. These data with the increased atopia/allergy in the studied infants suggest the need of a long-term follow-up for Treg cells and the advent of immune dysregulation events. Antimycobacterial response was diminished in exposed infants and not totally recovered after washing the drug from the blood in the culture. On the other hand, coinciding with the decrease of the drug levels in blood, the production of IL-12, IFN-γ and TNF-α increased. We conclude that the effects of anti-TNF-α exposure during pregnancy are not permanent and that BCG vaccination in these population should be avoided until, at least, 12 months of age.
By last, the transition between the intra- and extra-uterine world is a special life-situation where the immune system plays a major role. We studied it in healthy cord blood donors, with special
attention to the IL-12/IFN-γ pathway and B cell compartment, including regulatory B cells (Breg). Breg cells, defined as CD24hiCD38hi B cells, were expanded in cord blood, with capacity to produce IL-10 and to inhibit IL-4 and IFN-γ production by T cells with a similar phenotype when compared with adult Bregs. Besides, response to mycobacterial challenge was diminished. Interestingly, the diminished production of IFN-γ was associated with Breg cell frequency, opening the door to new research studying the role of these cells in different neonatal conditions as well as in cord blood derived stem cell transplantation.Esta tesis explora la vía de IL-12/IFN-g, central en la inmunidad a gérmenes intramacrofágicos, en el contexto de defectos primarios y secundarios. Los defectos primarios en esta vía causan susceptibilidad mendeliana a las micobacterias (MSMD), una inmunodeficiencia primaria que cursa con susceptibilidad a micobacterias no patogénicas principalmente, pero en la que se han descrito pacientes con infecciones por Mycobacterium tuberculosis y con leishmaniasis. En este escenario, la hemos estudiado en pacientes pediátricos con tuberculosis extrapulmonar y leishmaniasis visceral, revelando que no existían defectos completos de la vía, pero sí una alteración funcional en ésta en los dos grupos de pacientes estudiados. Esto reveló la necesidad de un estudio genético exhaustivo para revelar defectos parciales causantes de esta susceptibilidad. El diagnóstico la deficiencia de IL-12Rβ1 en una niña con infección diseminada por BCG, inicialmente diagnosticada como tuberculosis multirresistente, permitió el tratamiento adecuado que llevó a su curación, mostrando la relevancia del diagnóstico temprano del MSMD. Por otro lado, el hecho que se describiera un caso de muerte tras la vacunación con BCG de un neonato expuesto a fármacos anti-TNF-α durante el embarazo hizo pensar que la exposición a estos fármacos durante el embarazo pudiera llevar a defectos en el sistema inmunitario del neonato. Tras su estudio, observamos una inmadurez transitoria del compartimiento B y T; por otro lado, la disminución de la frecuencia de células T reguladoras que no normalizó con la edad juntamente con un aumento de la presencia de atopia o alergia en este grupo. Además, observamos una disminución de la respuesta a micobacterias en los niños expuestos, que mejoró con la edad. Concluimos que los efectos de los niños expuestos a anti-TNF-α durante el embarazo no parecen ser permanentes y que la vacunación con BCG de esta población debe ser evitada hasta los 12 meses de edad. El estudio de sangre de cordón de neonato sano reveló un aumento de la población de células B reguladoras. Además, la frecuencia de estas células se asoció inversamente con la producción de IFN-γ tras el estímulo con micobacterias, que se encontró disminuido en el neonato. Abriendo la puerta a nuevas investigaciones para estudiar su papel en diferentes condiciones del neonato, así como en el trasplante de progenitores hematopoyéticos.
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Killip, Marian J. "RNA virus modulation of IFN, PI3K and apoptosis." Thesis, St Andrews, 2009. http://hdl.handle.net/10023/777.
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Zurney, Jennifer Michelle. "Cardiac Cell Type-Specific Differences in the Interferon (IFN) Response, and Reovirus Repression of IFN." NCSU, 2008. http://www.lib.ncsu.edu/theses/available/etd-06302008-141954/.
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Viral myocarditis is an important human disease associated with a wide variety of viruses. The cardiac damage and inflammation associated with viral myocarditis can be immune mediated and/or due to direct cytopathic effect. Reovirus-induced myocarditis reflects direct virus-mediated apoptosis of cardiac cells, providing an excellent model to study direct cytopathic effect in the heart. Previous work has found interferon-beta (IFN) to be an important determinant for protection against viral myocarditis. Importantly, IFN signals through the Jak-STAT pathway to induce the expression of interferon-stimulated genes (ISGs) and establish an antiviral state. First, we investigated the underlying mechanisms of the IFN response in these cardiac cells. We found that high basal IFN-beta expression in cardiac myocytes protects this vulnerable, nonreplenishable cardiac cell type, while high basal expression of interferon alpha receptor 1 and latent Jak-STAT components in adjoining cardiac fibroblasts renders these cells more responsive to IFN and prevents them from inadvertently serving as a virus reservoir. This provides the first evidence for an integrated network of cell-type-specific innate immune components for organ protection. Next, we investigated whether particular reovirus strains were able to repress IFN signaling. We found that the mildly myocarditic reovirus, T1L, but not the nonmyocarditic reovirus, T3D, could repress IFN induction of ISGs and that this repressor function is determined by the M1 gene of T1L. Infection with T1L or reassortant or recombinant viruses containing the T1L M1 gene results in accumulation of IRF9 in the nucleus; an effect not previously described for any virus. The M1 gene has also previously been identified as a determinant of virus strain-specific differences in the IFN response, and the M1 gene and the IFN response have been identified as determinants of virus strain-specific differences in induction of murine myocarditis. Here, we find that virus-induced myocarditis is associated with repression of IFN function, providing new insights into the pathophysiology of this disease. Together, these data provide the first report of an increase in IRF9 nuclear accumulation associated with viral subversion of the IFN response, and provide evidence that virus strain-specific differences in IFN antagonism are a determinant of disease.
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Antoniazzi, Alfredo Quites. "Função endócrina do interferon-tau durante o reconhecimento materno da gestação em ovinos." Universidade Federal de Santa Maria, 2010. http://repositorio.ufsm.br/handle/1/4049.
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Conselho Nacional de Desenvolvimento Científico e TecnológicoThe objective of the present study is to evaluate interferon-tau (IFNT) endocrine action in extra uterine tissues. The first approach consists of collecting samples from ewes on days 12, 13, 14 and 15 of the estrous cycle or early pregnancy. The second, consists of installing osmotic pumps to deliver a continuous concentration of recombinant ovine (ro) IFNT into the uterine vein for 24 or 72 hours. Our hypothesis is that endocrine release of IFNT into the uterine vein occurs as early as Day 13 of pregnancy. Also, that 24 and 72 hours infusion of roIFNT induces ISGs in the CL, liver and endometrium and IFNT has endocrine action on the CL to modulate major genes involved in luteolysis. Endometrium, liver, corpus luteum, uterine vein, jugular and uterine vein blood were collected from cyclic (NP) and pregnant (P) ewes on Days 12, 13, 14 and 15. Instalation of 24 and 72 hour pumps was done on Day 10 of the estrous cycle. Half were infused with BSA and the other half with roIFNT. Only in the 24 hour infusion, half of each group was challanged with a PGF injection at 12 hours following pump installation. Concentrations of progesterone in serum were similar on Days 12 and 13 and then declined (P<0.05) to less than 1 ng/ml in NP ewes between Days 14 and 15. Endometrial ISG15 mRNA increased (P<0.05) in P versus NP ewes by Day 13 and remained greater through Day 15. Endometrial ESR1 and OXTR mRNAs were up-regulated (P<0.05) in NP compared to P ewes by Day 14, and remained up-regulated on Day 15. Uterine vein ISG15 mRNA was not affected by pregnancy status. IFNAR1 and IFNAR2 mRNA were present in the CL, but did not change due to pregnancy status. ISG15 mRNA in CL and liver increased (P<0.05) by Day 14 and remained up-regulated on Day 15 in P compared to NP ewes. The expression of ESR1, OXTR, PTGFR, PTGER2, PTGER3 and PTGER4 did not change in the corpus luteum during Days 12, 13, 14 and 15 related to pregnancy status. Following the 24 hour infusion, ESR1, OXTR, PTGER2 and PTGER3 mRNA were not affected, but SLCO2A1 mRNA decreased (P<0.001) in BSA+PGF, roIFNT and roIFNT+PGF compared to BSA-infused ewes. PTGFR mRNA was down regulated (P<0.001) in roIFNT and roIFNT+PGF compared to BSA and BSA+PGF-infused ewes. PTGER4 mRNA was greater (P<0.05) in roIFNT and roIFNT+PGF compared to BSA, but not compared to BSA+PGF-infused ewes. After 72 hours, concentrations of progesterone did not differ in roIFNT- compared to BSA-infused ewes. ISG15 mRNA was induced in the CL, liver and endometrium in roIFNT- compared with BSA-infused ewes. Endocrine action of IFNT occurred through up-regulation of ISG15 mRNA in CL and liver by Day 14 of pregnancy. It is concluded that IFNT has endocrine effects on the CL between Days 13 and 14 of pregnancy and may protect the CL through mechanisms that are complementary, yet independent to its paracrine effects on the OXTR endometrial pathway.
O objetivo deste trabalho foi avaliar a resposta do interferon-tau (IFNT) em tecidos extra uterinos utilizando dois modelos experimentais. O primeiro, com a utilização de amostras coletadas nos dias 12, 13, 14 e 15 do ciclo estral ou da gestação e o segundo com a instalação de bombas osmóticas de infusão contínua por 24 ou 72 horas. Formulou-se a hipótese que o IFNT é liberado na veia uterina em torno do dia 13 da gestação. Também, que após 24 ou 72 horas de infusão na veia uterina, o interferon-tau é capaz de induzir a expressão de genes estimulados pelo interferon (ISGs) no corpo lúteo, fígado e endométrio. A resposta no corpo lúteo é capaz de modular genes envolvidos na luteólise. Para isso, foram coletados endométrio, corpo lúteo, fígado, veia uterina, sangue das veias jugular e uterina, nos dias 12, 13, 14 e 15 do ciclo estral ou gestação. A instalação das bombas osmóticas de infusão por 24 e 72 horas foi realizada no dia 10 do ciclo estral, onde metade dos animais receberam infusão de albumina bovina (grupo BSA) e outra metade de IFNT recombinante ovino (ro; grupo roIFNT). Nos animais infundidos por 24 horas, metade de cada grupo BSA ou roIFNT, recebeu um desafio com prostaglandina F2 alfa (PGF; grupos BSA+PGF e roIFNT + PGF) 12 horas após a instalação das bombas. Concentrações sericas de progeterona foram iguais nos dias 12 e 13, e diminuiram (P<0,05) a menos de 1 ng/ml entre os dias 14 e 15 nos animais cíclicos. A expressão de ISG15 endometrial aumentou (P<0,05) no dia 13 em ovelhas prenhes, e permaneceu elevada até o dia 15. A expressão dos receptores de estrógeno alfa (ESR1) e de ocitocina (OXTR) aumentaram (P<0,05) em ovelhas cíclicas comparadas com prenhes no dia 14, permanecendo elevadas no dia 15. A expressão de ISG15 na veia uterina não apresentou diferença em função da gestação. A expressão dos receptores de Interferon tipo I não apresentou diferença em função da prenhez no corpo lúteo. No corpo lúteo e fígado, a expressão de ISG15 aumentou no dia 14 da gestação, permanecendo no dia 15. A expressão luteal de ESR1, OXTR, receptores de PGF (PTGFR), e E2 subtipos 2 (PTGER2), 3 (PTGER3) e 4 (PTGER4) não apresentaram diferença em função da gestação nos dias 12, 13 14, e 15. Após 24 horas de infusão, a expressão luteal de ESR1, OXTR, PTGER2 e PTGER3, não apresentaram diferenças. O transportador de prostaglandinas diminuiu nos grupos BSA+PGF, roIFNT e roIFNT+PGF (P<0,001). O receptor PTGFR diminuiu a expressão (P<0,001) nos grupos roIFNT e roIFNT+PGF, e o receptor PTGER4 aumentou (P<0,05) nos grupos roIFNT e roIFNT+PGF. Em 72 horas de infusão, não foi observada diferença na secreção de progesterona. A expressão de ISG15 nos animais do grupo roIFNT aumentou (P<0,01) no corpo lúteo, fígado e endométrio. Assim, a função endócrina do IFNT ocorre com a expressão de ISG15 no dia 14 da gestação no corpo lúteo e no fígado. Portanto, a ação endócrina do IFNT acontece entre os dias 13 e 14 da gestação e pode proteger o corpo lúteo por mecanismos complementares ao mecanismo anti luteolítico parácrino endometrial.
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SANTOS, Joelma Carvalho. "Análise de polimorfismos de único nucleotíldeo (SNP) e expressão dos genes das citocinas IFN-a1, IFN-y e do receptor IFN-a r1 em relação à quantificação da carga viral em pacientes com hepatite B." Universidade Federal de Pernambuco, 2014. https://repositorio.ufpe.br/handle/123456789/11489.
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A presença de polimorfismos de único nucleotídeo (SNPs) e a expressão variante dos genes das citocinas IFN-α1, IFN-γ e do receptor IFN-α r1 em pacientes com infecção crônica pelo vírus da hepatite B (HBV), podem ser considerados fatores etiopatogênicos relacionados aos níveis séricos do HBV, resultando em complicações da doença. Desta forma, o presente estudo teve como objetivo verificar a associação entre as frequências genotípicas e proporções alélicas dos genes IFNG, IFNA1, IFNAR1 em relação aos níveis de expressão desses genes e à carga viral do HBV, em pacientes com infecção crônica pelo HBV sem tratamento antiviral. Foi realizado um estudo de caso-controle com amostras de sangue total de 208 indivíduos (94 pacientes com infecção crônica e 114 indivíduos imunes ao HBV) no período de outubro de 2012 a agosto de 2013, no ambulatório de hepatologia do Hospital das Clínicas da Universidade Federal de Pernambuco (HC/UFPE) e no Hospital Escola Dr. Helvio Auto da Universidade Estadual de Ciências da Saúde de Alagoas (HEHA/UNCISAL). Para a identificação dos polimorfismos foi utilizada a PCR em tempo real (qPCR) de acordo com técnica de alta resolução de melting (HRM). A quantificação da carga viral e a expressão absoluta dos genes IFNG (-5 A>G), IFNA1 (-2 C>T), IFNAR1 (-97 T>C) foram realizadas por qPCR. Em todos os pacientes com infecção crônica pelo HBV os níveis de expressão foram menores para o gene IFNA1 (mediana=2,56x10-1ηg/μL), em relação aos genes IFNG (mediana=4,54x105ηg/μL) e IFNAR1 (mediana=6,92x109ηg/μL), e a média de carga viral foi de 3,2 log10. Pacientes com genótipo heterozigoto IFNA1(-2) CT e alelo polimórfico IFNA1 (-2) T apresentaram maiores chances de desenvolver proteção pelo HBV quando comparados a indivíduos imunes com genótipo IFNA1(-2) CC e alelo tipo selvagem C, respectivamente (IFNA1 CT/CC: OR=0,45; p=0,01 e IFNA T/C: OR=0,54; p<0,01). Em pacientes com infecção crônica e genótipo tipo selvagem TT do IFNAR1, os baixos níveis de expressão do gene desse receptor, quando comparado aos outros genótipos, explicam em 40% os altos níveis de carga viral desses pacientes (r2=0,40 | p=0,04) conferindo um risco para o desenvolvimento da cronicidade. Para o genes IFNG(-5) não foi observada diferença estatisticamente significante entre os níveis de expressão e os genótipos. Assim, a presença da variante polimórfica do gene IFNA1 (-2) em pacientes com infecção crônica, pode estar associada à proteção da cronicidade quando comparada ao grupo controle. Os altos níveis de expressão do gene IFNAR1 e baixos níveis de IFNA1 podem contribuir para a cronicidade nestes indivíduos. Os pacientes que com genótipo polimórfico IFNA1 (-2) CT e alelo T apresentaram maior proteção para a cronicidade pelo HBV.
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Chao, Ping. "Molecular basis of PKR activation by Interferon-gamma (IFNγ) mRNA 5’-UTR." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/molecular-basis-of-pkr-activation-by-interferongamma-ifn-mrna-5utr(76530b0e-e02f-4d59-8d38-4a2ba46fe741).html.
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PKR is an interferon (IFN)-induced protein kinase that is activated by double-stranded RNA in a mechanism involving binding of the N-terminal domain of PKR, protein dimerization and autophosphorylation. PKR is a key component of the cellular antiviral response and plays critical roles in a variety of other cellular processes including signal transduction, growth and apoptosis. Once activated, PKR phosphorylates its substrate, translation initiation factor (eIF2) on its alpha subunit at Ser51, thereby leading to an inhibition of protein synthesis. The IFN-gamma mRNA 5’-UTR, an H-type pesudoknot structure, is also a PKR activator. Activation through this structure thus and inhibition of translation thus autoregulates of overexpression of the IFN-gamma mRNA.Herein, I present a biochemical and biophysical characterization of the interaction between PKR and IFN-gamma mRNA 5’-UTR. In vitro PKR autophosphorylation assays defined that the minimal requirement of IFN-gamma mRNA 5’-UTR domain for PKR autophosphorylation is a 120 nt fragment that also exhibits the pseudoknot conformation. Additionally, mutations to disrupt IFN-gamma mRNA pseudoknot base pairing and stability decreased the ability to induce PKR autophosphorylation. Interaction of IFN-gamma 120 RNA and PKR appears to exhibit a ~1:2 binding stoichiometry. These results show that IFN-gamma mRNA binding to PKR is in agreement with other PKR activators; binding of dsRNA to PKR promotes dimerization and autophosphorylation.
Book chapters on the topic "Interferony (IFNy)"
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Stamatiadis-Smidt, Hilke, and Harald zur Hausen. "Interferone (IFN)." In Thema Krebs, 158–60. Berlin, Heidelberg: Springer Berlin Heidelberg, 1998. http://dx.doi.org/10.1007/978-3-662-10418-7_41.
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Obert, Hans-Joachim, and Dieter Pöhlau. "Dosierungsschemata für IFN-β." In Beta-Interferon, 165–86. Berlin, Heidelberg: Springer Berlin Heidelberg, 2000. http://dx.doi.org/10.1007/978-3-642-59764-0_4.
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Pfeffer, Lawrence M., David B. Donner, Tsutomu Arakawa, Nowell Stebbing, and Igor Tamm. "Early Events in the Interaction of IFN-α with IFN-Sensitive and IFN-Resistant Daudi Cells." In The Biology of the Interferon System 1986, 99–105. Dordrecht: Springer Netherlands, 1987. http://dx.doi.org/10.1007/978-94-009-3543-3_15.
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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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Knight, E., D. Fahey, R. Kutny, and D. C. Blomstrom. "Characterization of Two New IFN-Induced Proteins." In The Biology of the Interferon System 1986, 93–98. Dordrecht: Springer Netherlands, 1987. http://dx.doi.org/10.1007/978-94-009-3543-3_14.
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Diez, R. A., B. Perdereau, M. C. Martyre, J. Wietzerbin, S. Cornaert, M. Peter, C. Gaudelet, et al. "Pharmacokinetics of [123I]-Interferon (IFN) Alpha-A." In The Biology of the Interferon System 1986, 549–56. Dordrecht: Springer Netherlands, 1987. http://dx.doi.org/10.1007/978-94-009-3543-3_75.
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Parker, Dane. "Activation of Type I IFN Signaling by Staphylococcus aureus." In Bacterial Activation of Type I Interferons, 61–69. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-09498-4_5.
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Schlee, M., W. Barchet, V. Hornung, and G. Hartmann. "Beyond Double-Stranded RNA-Type I IFN Induction by 3pRNA and Other Viral Nucleic Acids." In Interferon: The 50th Anniversary, 207–30. Berlin, Heidelberg: Springer Berlin Heidelberg, 2007. http://dx.doi.org/10.1007/978-3-540-71329-6_11.
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Brosjö, Otte, Henrik C. F. Bauer, Olle S. Nilsson, and Hans Strander. "IFN-Gamma Inhibits Osteosarcoma Xenografts in Nude Mice." In The Biology of the Interferon System 1986, 301–4. Dordrecht: Springer Netherlands, 1987. http://dx.doi.org/10.1007/978-94-009-3543-3_42.
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Takaku, F. "Treatment of Various Malignancies with Recombinant IFN-γ." In The Biology of the Interferon System 1986, 415–21. Dordrecht: Springer Netherlands, 1987. http://dx.doi.org/10.1007/978-94-009-3543-3_56.
Full textConference papers on the topic "Interferony (IFNy)"
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Gamba, G., L. Dezza, N. Montani, G. Gangale, G. Gangale, and E. Ascari. "EFFECT OF INTERFERON GAMMA ON PROCOAGULANT ACTIVITY FROM HUMAN PROMYELOCYTIC CELL LINE (HL 60)." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643662.
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Interferon gamma (IFN), a lymphokine acting as biological response modifier, can induce morphological and phenotypic differentiation of some leukemic cell lines, specially along the monocytic pathway.Furthermore, myeloid leukemic cells and normal monocytes have been demonstrated to possess procoagulant activity (PCA).The aim of this study was to investigate the modulation of PCA induced by treatment with IFN on human promyelocytic cells from HL 60 cell line.Cells were cultured in suspension for 5days in RPMI 1640 medium supplemented with 10% fetal calf serum in the absence or in the presence of different concentrations of IFN (100-10.000 u/ml) at37°C and 5% CO2 Differentiation was assessed by morphological and cytochemical methods (MGG, ANAE, CAE, MPO) on cytospin preparations and surface marker analysis with monoclonal antibodies (0KMI, Mo2, MY9, MY7, MY4).PCA was measured as capacity to shortening ricalcification time of normal plasma and of factor VIII, VII and X deficient plasmas by the cells and the conditioned media.Untreated HL 60 cells exhibit high tissue factor-like PCA, related to the cellnumber. IFN treatment (1000 u/ml) induced at the same time, monocytic differentiation and significant increase in PCAboth in the cells and in the conditioned media.The PCA was not further affected by higher concentrations of IFN, unabletodetermine cell maturation.In conclusions the modulation by IFN seems to be dependent onmonocytic differentiation of HL 60 cells.
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"Interferon Gamma Levels in Relation to COVID-19 Vaccine." In 4th International Conference on Biological & Health Sciences (CIC-BIOHS’2022). Cihan University, 2022. http://dx.doi.org/10.24086/biohs2022/paper.691.
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One-hundred and twenty cases studied in this study for whom they take vaccine dose or not, for infected and non-infected with coronavirus. They are classified to four groups (Covid-19 – Non-Vaccinated = CN); (Covid-19 – Vaccinated = CV); (Non Covid-19 – Non-Vaccinated = NN); (Non-Covid-19 – Vaccinated = NV) each group involved 30 cases. After withdrawing the blood from each person, the blood poured into two tube (5 ml to Gel tube and 2 ml to EDTA tube) and immunological parameters directly performed by hematological analyzer, while the serum, after centrifugation of blood and storing them in special tubes, used to estimation of IFN- γ by Enzyme Linked Immunosorbent Assay (ELIZA) and Lactate Dehydrogenase (LDH) by chemical analyzer. The study showed that there is a slight increasing in IFN- γ as pro-inflammatory cytokine and LDH concentration which related to the severity of the disease, while there is rising in WBC number both vaccinated groups and cases with COVID-19 infection.
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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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Gugliotta, L., S. Macchi, L. Catani, M. Mattioli Belmonte, L. Gaggioli, and S. Tura. "EVALUATION OF THROMBOPOIESIS IN ESSENTIAL THROMBOCYTHAEMIA BEFORE AND AFTER α-INTERFERON TREATMENT." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644579.
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The α-interferon (α-IFN) has been shown efficacious in controlling thrombocytosis in chronic myeloproliferative disorders. In order to better understand the mechanisms by which this effect is produced, the main parameters of thrombopoiesis have been evaluated in 8 patients with Essential Thrombocythaemia (ET)just before and at the end of induction therapy with α-IFN. The patients, 2 males and 6 females, 17-54 years old, at diagnosis or at least 3 months off cytotoxic drugs, received α-IFN (Roferon A-Roche) s.c. at a daily dose of 3 × 106 IU for 6-13 weeks. The baseline platelet count of 993±266×109/1 fell, after treatment, to a value of 377±96×109 /1. The histological analysis of the bone marrow showed that the number of megakaryocytes (MK), initially 5-15 times the normal value (N), decreased to a value of 3-6 × N, while the MK volume resulted always high. The "in vitro" study of megakaryocytopoiesis, by the plasma-clot culture technique, documented a significant decrease of the number of MK colonies (from 73±18 to 29±15; p <0.0001). The half life-span of autologous platelets labelled withulIn-oxine remained unchanged (97±22 and 101±25 hours before and after therapy, respectively), while the platelet function abnormalities (hypo-aggregation, storage pool deficiency, etc) appeared less severe after treatment.It is concluded that in ET the α-IFN therapy is able to normalize the platelet count mainly or exclusively by a decrease of platelet production.The work was supported in part by grant of National Research Council (CNR), special Project Oncology No 85.02200.44.
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Wang, Wei, Hamada A. Aboubakr, James Vang, Victor Brenk, Sagar M. Goyal, and James Collins. "Nanomagnetic Biosensor for the Detection of Porcine Interferon Gamma." In 2017 Design of Medical Devices Conference. American Society of Mechanical Engineers, 2017. http://dx.doi.org/10.1115/dmd2017-3375.
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Due to the anatomical and physiological similarities to humans that include similar heart size, flow rate, skin, liver enzymes and bone healing, porcine models as a powerful investigational platform have been widely used in research areas such as diabetes, obesity and islet transplantation [1]. The advantages of relative low cost, ease in handling and comparatively short period of breeding time may make swine provide a promising solution to the shortage of human donors and difficulty in isolating purified islets from adult human in future. Porcine cytokines play a significant role in innate immunity, apoptosis, angiogenesis, cell growth and differentiation. They are involved in cellular responses, maintenance of homeostasis, and disease states such as inflammatory disease, cardiovascular disease, and cancer. Thus, the technologies to analyze the expression of cytokines are developed rapidly and are still hot topics. The traditional approach for cytokine detection and quantification is the use of an enzyme-linked immunosorbent assay (ELISA). However, its inability to do multiplex test calls for more robust detection system. Biochip-based assay for the detection of biological agents using giant magnetoresistive (GMR) sensors and magnetic nanoparticles have emerged recently [2, 3]. It is proved that the nanomagnetic biosensor technology has advantages of low cost, high sensitivity, multiplexity, and real-time signal readout. The integration of GMR biosensor and use of weak magnetic fields allow to eventually realize point-of-care and portability. In addition, interferon gamma (IFNγ) is one of the most important porcine cytokines, and is associated with a number of autoinflammatory and autoimmune diseases. In this work, IFNγ is selected as a model target for the detection of porcine cytokine using nanomagnetic GMR biosensor.
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Sharma, Shashank, Fawzi Ali, Saikia Sujoy, and Karaj Jola. "Interferon gamma (IFN?) pathway deficiency and severe NTM disease." In ERS International Congress 2021 abstracts. European Respiratory Society, 2021. http://dx.doi.org/10.1183/13993003.congress-2021.pa3086.
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Vale, Paula Melo, Juliana Gonzaga Araújo Clark, Natália Campos Ramos, Rachel Calazans De Oliveira Costa Costa, and Sofia Assis Alvarenga. "O USO DE INTERFERON-BETA NO TRATAMENTO DE ESCLEROSE MÚLTIPLA." In I Congresso Brasileiro de Imunologia On-line. Revista Multidisciplinar em Saúde, 2021. http://dx.doi.org/10.51161/rems/981.
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Introdução: A Esclerose Múltipla (EM) é uma doença autoimune que acomete o sistema nervoso central (SNC), promovendo a destruição da bainha de mielina. É considerada rara, cuja epidemiologia é de 30 para 100.000 pessoas no mundo, sendo mais comum em mulheres. Essa doença apresenta como um dos sintomas mais recorrentes a fadiga, caracterizando-se pela dificuldade em manter a contração muscular. Também são relatados sintomas como astenia, neurite óptica, paresia ou parestesia de membros, disfunção da coordenação e equilíbrio, mielites, disfunções esfincterianas e disfunções cognitivo comportamentais. A fisiopatologia da doença é pouco conhecida, mas evidências indicam que a EM é causada por células Th1 e Th17, que reagem contra antígenos próprios da mielina, resultando na inflamação do SNC com ativação de macrófagos ao redor dos nervos, do cérebro e da medula espinhal, destruição da mielina e anormalidades na condução nervosa. O diagnóstico é feito pela avaliação clínica e por exames complementares, sendo a ressonância magnética o padrão-ouro. Uma das terapias utilizadas para EM é a administração de Interferon-Beta (IFN-β), possuindo papel modulador na resposta inflamatória desencadeada pela imunidade celular no SNC. Objetivo: Discutir sobre o tratamento alternativo da Esclerose Múltipla com Interferon-Beta, compreendendo o mecanismo de ação dessa citocina na doença. Material e Métodos: Revisão bibliográfica integrativa de estudos nas bases de dados Scielo, Pubmed e BVS, com os descritores "esclerose múltipla", "interferon beta" e "tratamento". Resultados: Foram analisados oito estudos sobre o tratamento da EM pelo IFN-β; a maioria deles relata a satisfação dos pacientes com esse medicamento, além de se mostrar eficiente na diminuição dos surtos e sintomas da doença. Dentre os principais resultados da terapia com INF-β, nota-se a redução de citocinas pró-inflamatórias e o aumento de citocinas anti-inflamatórias, o que confirma a sua eficácia como imunomodulador. Conclusão: A esclerose múltipla está entre as mais vulneráveis das doenças neurológicas devido à sua cronicidade e ao acometimento de adultos jovens. Em relação ao tratamento, o uso de imunomoduladores têm sido eficaz, sendo o IFN-β uma opção muito utilizada. Observa-se a redução do número de surtos em parcela significativa desses pacientes, além da progressão mais lenta da doença.
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Cakebread, JA, Y. Xu, D. Sammut, P. Howarth, ST Holgate, and DE Davies. "Antiviral Effects of Interferon beta (IFNβ) in Asthmatic Bronchial Epithelial Cell Cultures." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a5171.
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Ригер, Николай Александрович, Элеонора Николаевна Трушина, and Андрей Николаевич Тимонин. "INFLUENCE OF HIGH PHYSICAL LOADS ON THE IMMUNOREGULATORY STATUS OF ATHLETES." In Сборник избранных статей по материалам научных конференций ГНИИ "Нацразвитие" (Санкт-Петербург, Август 2022). Crossref, 2022. http://dx.doi.org/10.37539/aug304.2022.84.56.002.
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В статье приводятся данные изучения цитокинового профиля (определение уровней содержания интерлейкинов: IL-4, IL-10, IL-18 и γ-интерферона (γ-IFN) методом твердофазного иммуноферментного анализа у17 спортсменов - биатлонистов высшей спортивной квалификации и 17 здоровых добровольцев со средней физической активностью. Полученные результаты подтверждают значительную вариабельность содержания иммунорегуляторных цитокинов в сыворотке крови здоровых людей. Повышение уровней провоспалительных цитокинов у спортсменов свидетельствует о напряженности иммунного ответа при интенсивных физических нагрузках. The article presents the data of the study of the cytokine profile (determination of the levels of interleukins: IL-4, IL-10, IL-18 and γ-interferon (γ-IFN) by enzyme-linked immunosorbent assay in 17 athletes - biathletes of the highest sports qualification and 17 healthy volunteers with moderate physical activity. The results confirm significant variability in the content of immunoregulatory cytokines in the blood serum of healthy people. An increase in the levels of pro-inflammatory cytokines in athletes indicates the immunity tension during high-intensity exercise.
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Yamauchi, K., Y. Shibata, M. Sato, T. Kimura, D. Osaka, S. Inoue, S. Abe, and I. Kubota. "Reduced IL-12p40 Signaling with Azithromycin (AZM) in Lipopolysacchalide (LPS) and Interferon (IFN)-γ Stimulated Macrophages." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a1938.
Full textReports on the topic "Interferony (IFNy)"
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Chen, Cheng-Che, and Hao-En Lin. Survival Benefits and Bleeding Risk of Anti-VEGF Agents for Renal Cell Carcinoma (RCC): A Updated Systematic Review and Meta-Analysis of Phase 2 and 3 Randomized Clinical Trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, March 2023. http://dx.doi.org/10.37766/inplasy2023.3.0007.
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Review question / Objective: To investigate the survival benefits (PFS, DFS, OS) and bleeding risk of the anti-VEGF agents compared with placebo or interferon alpha (IFNa) in patients with RCC. Condition being studied: Part 1. The hazard ratio (HR) of the progression-free survival (PFS) and overall survival (OS) of anti-VEGF agents vs. non/placebo for patients with unresectable, advanced, metastatic, renal cell carcinoma (RCC). Part 2. The HR of the disease-free survival (PFS) and OS of anti-VEGF agents vs. non/placebo for patients with post-nephrectomy RCC (adjuvant use). Part 3. The HR of the PFS and OS of anti-VEGF agents vs. IFN-alpha for patients with RCC. Part 4. The relative risk (RR) of bleeding events of anti-VEGF agents vs. placebo or IFN-alpha for patients with RCC.