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  • 1
    ISSN: 1432-1211
    Keywords: Key words Interferon gamma ; Polymorphism ; Promoter ; AIOS ; 3′UTR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Interferon gamma (IFN-gamma) is a multifunctional cytokine that is essential in the development of Th1 cells and in cellular responses to a variety of intracellular pathogens including human immunodeficiency virus (HIV-1). We screened genomic DNA samples from a predominately Caucasian male population of HIV-infected and healthy donors for polymorphisms in the human IFNG gene from –777 to +5608 by single-stranded conformational polymorphism. Surprisingly, the proximal promoter (–777 to transcription start) is invariant as no polymorphisms were found in over 100 samples tested. However, further screening revealed polymorphisms in other regions of the gene including a single base insertion in a poly-T tract in the first intron, three single base pair substitutions in the third intron, and another single base pair substitution in the 3′ untranslated region (UTR). Electrophoretic mobility shift assay was used to investigate whether these variants have altered DNA-binding abilities, since intronic enhancer elements have been reported for the IFNG gene. Oligonucleotides constructed for two third intron variants showed no difference in DNA-binding abilities as compared with wild-type sequences. However, the 3′UTR variant showed the formation of unique DNA-binding complexes to radiolabeled oligonucleotide probes as compared with the wild-type sequence. The influence of a CA-repeat microsatellite on AIDS disease progression in HIV-1 seroconverters was tested by a Cox proportional hazards model. There is no evidence of an association between alleles and infection with HIV-1 or progression to AIDS. We report an invariant proximal human IFNG promoter and the existence of multiple intronic variants and a potentially functional 3′UTR polymorphism.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2018-03-07
    Description: Il10 forms a cytokine cluster with Il19 , Il20 , and Il24 in a conserved region of chromosome 1. The latter genes are in the IL-20 subfamily of IL-10–related cytokines and, although they are not as well studied their biologic actions and expression patterns, seem to have little in common with IL-10. IL-24, like IL-10, however, is uniquely expressed in T cells and is a signature gene of the Th2 lineage, which suggests they could be coregulated in certain cell types. Little is known about other cellular sources of IL-24. We investigated IL-24 and IL-10 expression in murine macrophages and NK cells, and found that although they are coexpressed under most stimulation conditions, IL-24 and IL-10 are controlled by distinct, cell type–specific pathways. In bone marrow–derived macrophages, optimal IL-24 expression required LPS+IL-4 costimulation and STAT6 but was independent of type I IFN receptor signaling and STAT4. Conversely, LPS-induced IL-10 was independent of IL-4/STAT6 and STAT4 but, consistent with other reports, required type I IFN receptor signaling for optimal expression. Remarkably, NK-specific IL-24 (but not IL-10) expression was dependent on both type I IFN receptor signaling and STAT4. Induction of IL-24 expression was accompanied by cell-specific recruitment of STAT6 and STAT4 to multiple sites that we identified within Il24 , which mediated STAT-dependent histone modifications across the gene. Collectively, our results indicate that despite being coexpressed, IL-10 and IL-24 are independently regulated by different type I IFN receptor signaling pathways in innate immune cells and provide insight into the mechanisms that fine-tune cell type–specific gene expression within the Il10 cluster.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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