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首页> 外文期刊>International journal of immunogenetics >The microsatellite, macrophage migration inhibitory factor -794, may influence gene expression in human mononuclear cells stimulated with E. coli or S. pneumoniae.
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The microsatellite, macrophage migration inhibitory factor -794, may influence gene expression in human mononuclear cells stimulated with E. coli or S. pneumoniae.

机译:微卫星巨噬细胞迁移抑制因子-794可能会影响大肠杆菌或肺炎链球菌刺激的人单核细胞中的基因表达。

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摘要

Polymorphisms within the gene encoding macrophage migration inhibitory factor (MIF) have been associated with susceptibility to inflammatory diseases such as rheumatoid arthritis and increased risk of developing sepsis. We investigated the effects of the MIF-173G>C polymorphism and the MIF-794 CATT microsatellite on MIF expression. These are in moderate linkage disequilibrium. Mononuclear cells from healthy donors were stimulated with bacterial pathogens associated with sepsis (Streptococcus pneumoniae or Escherichia coli ). MIF mRNA and protein levels were measured by real-time polymerase chain reaction and ELISA, respectively. Carriage of the C allele of MIF-173G>C or the 7 CATT repeat of the MIF-794 microsatellite correlated with lower basal and stimulated MIF mRNA levels. However, levels of intracellular and extracellular MIF protein were similar. This discordance between effects on MIF mRNA and protein was not explained by differential effects of genotype on stability of MIF mRNA (detected by actinomycin D mRNA chase). Gel shift assays revealed no differences in the profile of nuclear proteins from mononuclear cells bound by the G and C alleles of MIF-173G>C, but alleles at the microsatellite marker showed differential binding. Our data suggest that the MIF-794 CATT microsatellite influences transcription by differential binding of nuclear transcription factors. This may impact on inflammatory processes.
机译:编码巨噬细胞迁移抑制因子(MIF)的基因内的多态性与易感性疾病(如类风湿性关节炎)的易感性有关,并增加了发生败血症的风险。我们调查了MIF-173G> C多态性和MIF-794 CATT微卫星对MIF表达的影响。这些处于中等连锁不平衡状态。用与败血症相关的细菌病原体(肺炎链球菌或大肠杆菌)刺激健康供体的单核细胞。 MIF mRNA和蛋白质水平分别通过实时聚合酶链反应和ELISA测定。 MIF-173G> C的C等位基因的携带或MIF-794微卫星的7 CATT重复与较低的基础和受激的MIF mRNA水平相关。但是,细胞内和细胞外MIF蛋白的水平相似。基因型对MIF mRNA稳定性的不同影响(通过放线菌素D mRNA追踪检测)不能解释对MIF mRNA和蛋白质的影响之间的这种不一致。凝胶位移分析显示,与MIF-173G> C的G和C等位基因结合的单核细胞的核蛋白谱没有差异,但微卫星标记处的等位基因显示差异结合。我们的数据表明,MIF-794 CATT微卫星通过核转录因子的差异结合影响转录。这可能会影响炎症过程。

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