Millipore Sigma Vibrant Logo
 

ifn-


622 Results Búsqueda avanzada  
Mostrar
Productos (5)
Documentos (605)
Páginas (12)

Acote sus resultados Utilice los filtros siguientes para refinar su búsqueda

Tipo de documento

  • (467)
  • (87)
  • (38)
  • (4)
  • (4)
  • Mostrar más
¿No encuentra lo que está buscando?
Póngase en contacto con
el Servicio de Atención
al Cliente

 
¿Necesita ayuda para encontrar un documento?

  • CpG-B oligodeoxynucleotides inhibit TLR-dependent and -independent induction of type I IFN in dendritic cells. 20181884

    CpG oligodeoxynucleotides (ODNs) signal through TLR9 to induce type I IFN (IFN-alphabeta) in dendritic cells (DCs). CpG-A ODNs are more efficacious than CpG-B ODNs for induction of IFN-alphabeta. Because IFN-alphabeta may contribute to autoimmunity, it is important to identify mechanisms to inhibit induction of IFN-alphabeta. In our studies, CpG-B ODN inhibited induction of IFN-alphabeta by CpG-A ODN, whereas induction of TNF-alpha and IL-12p40 by CpG-A ODN was not affected. CpG-B inhibition of IFN-alphabeta was observed in FLT3 ligand-induced murine DCs, purified murine myeloid DCs, plasmacytoid DCs, and human PBMCs. CpG-B ODN inhibited induction of IFN-alphabeta by agonists of multiple receptors, including MyD88-dependent TLRs (CpG-A ODN signaling via TLR9, or R837 or Sendai virus signaling via TLR7) and MyD88-independent receptors (polyinosinic:polycytidylic acid signaling via TLR3 or ds break-DNA signaling via a cytosolic pathway). CpG-B ODN did not inhibit the IFN-alphabeta positive feedback loop second-wave IFN-alphabeta, because IFN-alphabeta-induced expression of IFN-alphabeta was unaffected, and CpG-B inhibition of IFN-alphabeta was manifested in IFN-alphabetaR(-/-) DCs, which lack the positive feedback mechanism. Rather, CpG-B ODN inhibited early TLR-induced first wave IFN-alpha4 and IFN-beta. Chromatin immunoprecipitation revealed that association of IFN regulatory factor 1 with the IFN-alpha4 and IFN-beta promoters was induced by CpG-A ODN but not CpG-B ODN. Moreover, CpG-A-induced association of IFN regulatory factor 1 with these promoters was inhibited by CpG-B ODN. Our studies demonstrate a novel mechanism of transcriptional regulation of first-wave IFN-alphabeta that selectively inhibits induction of IFN-alphabeta downstream of multiple receptors and may provide targets for future therapeutic inhibition of IFN-alphabeta expression in vivo.
    Tipo de documento:
    Referencia
    Referencia del producto:
    06-866
    Nombre del producto:
    Anti-acetyl-Histone H4 Antibody

  • Type I IFN operates pyroptosis and necroptosis during multidrug-resistant A. baumannii infection. 29352265

    Multidrug-resistant Acinetobacter baumannii, a common pathogen responsible for nosocomial infections, is the main cause for outbreaks of infectious diseases, such as pneumonia, meningitis, and bacteremia, especially among critically ill patients. Epidemic A. baumannii is a growing public health concern as it is resistant to all existing antimicrobial agents, thereby necessitating the development of new therapeutic approaches to mount an effective immune response against this bacterial pathogen. In this study, we identified a critical role for type I interferon (IFN) in epigenetic regulation during A. baumannii infection and established a central role for it in multiple cell death pathways. A. baumannii infection induced mixed cell death constituted of apoptosis, pyroptosis, and necroptosis. Mechanically, A. baumannii triggered TRIF-dependent type I IFN production, which in turn induced the expression of genes Zbp1, Mlkl, caspase-11, and Gsdmd via KAT2B-mediated and P300-mediated H3K27ac modification, leading to NLRP3 inflammasome activation, and potentially contributed to GSDMD-mediated pyroptosis and MLKL-dependent necroptosis. Our study offers novel insights into the mechanisms of type I IFN and provides potential therapeutic targets for infectious and inflammatory diseases.
    Tipo de documento:
    Referencia
    Referencia del producto:
    17-371
    Nombre del producto:
    EZ-ChIP™

  • IFITM3 inhibits influenza A virus infection by preventing cytosolic entry. 22046135

    To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB8800

  • The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. 12829834

    The Ebola virus VP35 protein was previously found to act as an interferon (IFN) antagonist which could complement growth of influenza delNS1 virus, a mutant influenza virus lacking the influenza virus IFN antagonist protein, NS1. The Ebola virus VP35 could also prevent the virus- or double-stranded RNA-mediated transcriptional activation of both the beta IFN (IFN-beta) promoter and the IFN-stimulated ISG54 promoter (C. Basler et al., Proc. Natl. Acad. Sci. USA 97:12289-12294, 2000). We now show that VP35 inhibits virus infection-induced transcriptional activation of IFN regulatory factor 3 (IRF-3)-responsive mammalian promoters and that VP35 does not block signaling from the IFN-alpha/beta receptor. The ability of VP35 to inhibit this virus-induced transcription correlates with its ability to block activation of IRF-3, a cellular transcription factor of central importance in initiating the host cell IFN response. We demonstrate that VP35 blocks the Sendai virus-induced activation of two promoters which can be directly activated by IRF-3, namely, the ISG54 promoter and the ISG56 promoter. Further, expression of VP35 prevents the IRF-3-dependent activation of the IFN-alpha4 promoter in response to viral infection. The inhibition of IRF-3 appears to occur through an inhibition of IRF-3 phosphorylation. VP35 blocks virus-induced IRF-3 phosphorylation and subsequent IRF-3 dimerization and nuclear translocation. Consistent with these observations, Ebola virus infection of Vero cells activated neither transcription from the ISG54 promoter nor nuclear accumulation of IRF-3. These data suggest that in Ebola virus-infected cells, VP35 inhibits the induction of antiviral genes, including the IFN-beta gene, by blocking IRF-3 activation.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MABF268
    Nombre del producto:
    Anti-IRF3 Antibody, clone SL-12

  • pp32, an INHAT component, is a transcription machinery recruiter for maximal induction of IFN-stimulated genes. 21325029

    Type I interferon (IFN) plays a crucial role in establishing the cellular antiviral state by inducing transcription of IFN-stimulated genes (ISGs). Generally, histone acetyltransferases (HATs) are positive regulators of transcription, but histone deacetylase (HDAC) activity is essential for transcriptional induction of ISGs. pp32 is known to be a key component of the inhibitor of acetyltransferase (INHAT) complex that inhibits HAT-dependent transcriptional activation. Here, we show that pp32 is involved in the positive regulation of ISG transcription. pp32 interacted with signal transducer and activator of transcription 1 (STAT1) and STAT2 in an IFN-dependent manner. pp32 was not required for tyrosine phosphorylation and nuclear translocation of STATs, but was needed for binding of transcriptional complexes with ISG promoters and, thereby, for maximal transcription activation. pp32 was found to be associated with ISG promoters in IFN-untreated cells, and its binding amount fluctuated as a function of time after IFN treatment. short interfering RNA (siRNA)-mediated knockdown of pp32 expression reduced the histone acetylation level on ISG promoters, suggesting that pp32 plays a role in ISG transcription by a function other than that of INHAT. Taking these findings together, we propose that pp32 is involved in the formation of ISG transcription initiation complexes, possibly as their recruiter.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo

  • Activation of the STING adaptor attenuates experimental autoimmune encephalitis. 24799564

    Cytosolic DNA sensing activates the stimulator of IFN genes (STING) adaptor to induce IFN type I (IFN-αβ) production. Constitutive DNA sensing to induce sustained STING activation incites tolerance breakdown, leading to autoimmunity. In this study, we show that systemic treatments with DNA nanoparticles (DNPs) induced potent immune regulatory responses via STING signaling that suppressed experimental autoimmune encephalitis (EAE) when administered to mice after immunization with myelin oligodendrocyte glycoprotein (MOG), at EAE onset, or at peak disease severity. DNP treatments attenuated infiltration of effector T cells into the CNS and suppressed innate and adaptive immune responses to myelin oligodendrocyte glycoprotein immunization in spleen. Therapeutic responses were not observed in mice treated with cargo DNA or cationic polymers alone, indicating that DNP uptake and cargo DNA sensing by cells with regulatory functions was essential for therapeutic responses to manifest. Intact STING and IFN-αβ receptor genes, but not IFN-γ receptor genes, were essential for therapeutic responses to DNPs to manifest. Treatments with cyclic diguanylate monophosphate to activate STING also delayed EAE onset and reduced disease severity. Therapeutic responses to DNPs were critically dependent on IDO enzyme activity in hematopoietic cells. Thus, DNPs and cyclic diguanylate monophosphate attenuate EAE by inducing dominant T cell regulatory responses via the STING/IFN-αβ/IDO pathway that suppress CNS-specific autoimmunity. These findings reveal dichotomous roles for the STING/IFN-αβ pathway in either stimulating or suppressing autoimmunity and identify STING-activating reagents as a novel class of immune modulatory drugs.
    Tipo de documento:
    Referencia
    Referencia del producto:
    ABN78
    Nombre del producto:
    Anti-NeuN Antibody (rabbit)

  • Recruitment of histone deacetylase 3 to the interferon-A gene promoters attenuates interferon expression. 22685561

    Induction of Type I Interferon (IFN) genes constitutes an essential step leading to innate immune responses during virus infection. Sendai virus (SeV) infection of B lymphoid Namalwa cells transiently induces the transcriptional expression of multiple IFN-A genes. Although transcriptional activation of IFN-A genes has been extensively studied, the mechanism responsible for the attenuation of their expression remains to be determined.In this study, we demonstrate that virus infection of Namalwa cells induces transient recruitment of HDAC3 (histone deacetylase 3) to IFN-A promoters. Analysis of chromatin-protein association by Chip-QPCR demonstrated that recruitment of interferon regulatory factor (IRF)3 and IRF7, as well as TBP correlated with enhanced histone H3K9 and H3K14 acetylation, whereas recruitment of HDAC3 correlated with inhibition of histone H3K9/K14 acetylation, removal of IRF7 and TATA-binding protein (TBP) from IFN-A promoters and inhibition of virus-induced IFN-A gene transcription. Additionally, HDAC3 overexpression reduced, and HDAC3 depletion by siRNA enhanced IFN-A gene expression. Furthermore, activation of IRF7 enhanced histone H3K9/K14 acetylation and IFN-A gene expression, whereas activation of both IRF7 and IRF3 led to recruitment of HDAC3 to the IFN-A gene promoters, resulting in impaired histone H3K9 acetylation and attenuation of IFN-A gene transcription.Altogether these data indicate that reversal of histone H3K9/K14 acetylation by HDAC3 is required for attenuation of IFN-A gene transcription during viral infection.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo

  • The type I interferon signaling pathway is a target for glucocorticoid inhibition. 20679482

    Type I interferon (IFN) is essential for host defenses against viruses; however, dysregulated IFN signaling is causally linked to autoimmunity, particularly systemic lupus erythematosus. Autoimmune disease treatments rely on glucocorticoids (GCs), which act via the GC receptor (GR) to repress proinflammatory cytokine gene transcription. Conversely, cytokine signaling through cognate Jak/STAT pathways is reportedly unaffected or even stimulated by GR. Unexpectedly, we found that GR dramatically inhibited IFN-stimulated gene (ISG) expression in macrophages. The target of inhibition, the heterotrimeric STAT1-STAT2-IRF9 (ISGF3) transcription complex, utilized the GR cofactor GRIP1/TIF2 as a coactivator. Consequently, GRIP1 knockdown, genetic ablation, or depletion by GC-activated GR attenuated ISGF3 promoter occupancy, preinitiation complex assembly, and ISG expression. Furthermore, this regulatory loop was restricted to cell types such as macrophages expressing the GRIP1 protein at extremely low levels, and pharmacological disruption of the GR-GRIP1 interaction or transient introduction of GRIP1 restored RNA polymerase recruitment to target ISGs and the subsequent IFN response. Thus, type I IFN is a cytokine uniquely controlled by GR at the levels of not only production but also signaling through antagonism with the ISGF3 effector function, revealing a novel facet of the immunosuppressive properties of GCs.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo

  • Type I IFN innate immune response to adenovirus-mediated IFN-gamma gene transfer contributes to the regression of cutaneous lymphomas. 17823660

    The fact that adenoviral vectors activate innate immunity and induce type I IFNs has not been fully appreciated in the context of cancer gene therapy. Type I IFNs influence different aspects of human immune response and are believed to be crucial for efficient tumor rejection. We performed transcriptional profiling to characterize the response of cutaneous lymphomas to intralesional adenovirus-mediated IFN-gamma (Ad-IFN-gamma) gene transfer. Gene expression profiles of skin lesions obtained from 19 cutaneous lymphoma patients before and after treatment with Ad-IFN-gamma revealed a distinct gene signature consisting of IFN-gamma- and numerous IFN-alpha-inducible genes (type II- and type I-inducible genes, respectively). The type I IFN response appears to have been induced by the vector itself, and its complexity, in terms of immune activation, was potentiated by the IFN-gamma gene insert. Intralesional IFN-gamma expression together with the induction of a combined type I/II IFN response to Ad-IFN-gamma gene transfer seem to underlie the objective (measurable) clinical response of the treated lesions. Biological effects of type I IFNs seem to enhance those set in motion by the transgene, in our case IFN-gamma. This combination may prove to be of therapeutic importance in cytokine gene transfer using Ads.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MABF938
    Nombre del producto:
    Anti-MxA, clone M143 (CL143)

  • Characterization of cytokine-producing cells in mucosal effector sites: CD3+ T cells of Th1 and Th2 type in salivary gland-associated tissues. 7957557

    The major purpose of this study was to elucidate Th1 [interferon (IFN)-gamma and interleukin (IL)-2] and Th2 (IL-4, IL-5 and IL-6) cytokine-producing CD3+ T cells in salivary glands, which are the major mucosal effector tissues in the oral region. Thus, CD3+ T cells were isolated from salivary gland-associated tissues (SGAT) which consist of the submandibular gland (SMG: approximately 46%), the periglandular lymph node (PGLN: approximately 72%), and the cervical lymph node (CLN: approximately 90%). When SMG CD3+ T cells were examined by Th1 and Th2 cytokine-specific ELISPOT and reverse transcriptase-polymerase chain reaction assay, high levels of both cytokine-specific spot-forming cells (SFC) and mRNA for IFN-gamma, and for IL-5 and IL-6 were noted as representative Th1 or Th2 cytokines, respectively. Following stimulation with concanavalin A (Con A), SMG CD3+ T cells expressed mRNA and produced lymphokines for an array of Th1 (IFN-gamma and IL-2) and Th2 (IL-4, IL-5 and IL-6) cytokines. In comparison to the SMG CD3+ T cells, PGLN and CLN contain lower numbers of IFN-gamma-, IL-5 and IL-6-producing T cells. When these two tissues were compared, PGLN CD3+ T cells contained higher numbers of cytokine-secreting cells than CLN. Further, IL-2 and IL-4 SFC and mRNA were also noted in addition to IFN-gamma, IL-5 and IL-6 after Con A activation. These findings showed that CD3+ T cells in SGAT, especially the SMG, are programmed to produce IFN-gamma, and IL-5 and IL-6 as Th1 and Th2 cytokines, respectively in vivo, although these cells are capable of producing other Th1 and Th2 cytokines after receiving appropriate T cell activation signals.
    Tipo de documento:
    Referencia
    Referencia del producto:
    17-191
    Nombre del producto:
    MAP Kinase/Erk Assay Kit, non-radioactive