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  • 1995-1999  (2)
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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In order to understand the molecular basis of the synergistic action of interferon γ (IFN-γ) and tumour necrosis factor α (TNF-α) on rat oligodendrocyte development, we studied some aspects of the signalling pathways involved in the regulation of the major histocompatibility complex (MHC) class I and the interferon regulatory factor 1 (IRF-1) gene expression. Two well-defined inducible enhancers of the MHC class I gene promoter, the MHC class I regulatory element (MHC-CRE) and the interferon consensus sequence (ICS), were analysed. Neither IFN-γ nor TNF-α was capable of inducing MHC-CRE binding activity when administrated alone. Following the exposure of oligodendrocytes to IFN-γ, TNF-R1 expression was transcriptionally induced by the binding of signal transducer and activator of transcription (STAT-1) homodimers to the IFN-γ activated site (GAS) present in the gene promoter. The upregulation of TNF-R1 allowed TNF-α to induce the binding of nuclear factor-κB (NF-κB) to the MHC-CRE site. With respect to ICS element, IFN-γ induced IRF-1 binding, that was further enhanced upon co-treatment with TNF-α. The existence of a synergism between IFN-γ and TNF-α in stimulating IRF-1 expression at the transcriptional level was supported by IRF-1 promoter analysis: IFN-γ directly induced the binding of STAT-1 homodimers to the GAS element, while NF-κB binding to the κB sequence was activated by TNF-α only after IFN-γ treatment. This transcriptional regulation of IRF-1 gene by IFN-γ and TNF-α was confirmed at the mRNA level. The synergism demonstrated in the present study highlights the importance of cytokine interactions in magnifying their biological effects during brain injury and inflammation.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary.  Two different strains of HIV-1, the lymphotropic HIV-IIIB and the monocytotropic HIV-Ba-L, were able to infect tertiary cultures of astrocytes established from the human embryonic brain. The infection did not require contact with infected cells, as astrocytes were exposed to infectious cell-free supernatants. Except for an early transient peak of p24 consistently observed after infection with HIV-Ba-L, the infection of astrocytes appeared to be nonproductive. However, viral production was always observed when infected astrocytes were cocultured with permissive cells (CEM-SS or monocytes). To exclude the possibility that undetectable levels of virus are chronically produced by astrocytes, we exposed permissive cells to p24 negative supernatants taken from infected cultures. In such conditions permissive cells were never infected. Infection of astrocytes by HIV-1 was further supported by the finding that provirus persisted in these cells. Indeed, by a nested PCR, we detected HIV-1 DNA even one month after infection. Moreover, at the transcriptional level we observed expression of the multiply spliced RNA (tat) and nef primers). Noteworthy, this pattern of HIV-1 expression did not change appreciably when astrocytes were pretreated and cultivated in the presence of IL-1β. Altogether, our data support the concept that astrocytes may play a role in the spread of HIV-1 infection within the brain and in the pathogenesis of neuro-AIDS.
    Type of Medium: Electronic Resource
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