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Global effect of PEG-IFN-alpha and ribavirin on gene expression in PBMC in vitro.

机译:PEG-IFN-α和利巴韦林对PBMC体外基因表达的整体影响。

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摘要

Using oligonucleotide microarrays, we have examined the expression of 22,000 genes in peripheral blood cells treated with pegylated interferon-alpha2b (PEG-IFN-alpha) and ribavirin. Treatment with ribavirin had very little effect on gene expression, whereas treatment with PEG-IFN-alpha had a dramatic effect, modulating the expression of approximately 1000 genes (at p < 0.001). In addition to genes previously reported to be induced by type I or type II IFNs, many novel genes were found to be upregulated, including transcription factors, such as ATF3, ATF4, properdin, a key regulator of the complement pathway, a homeobox gene (HESX1), and an RNA editing enzyme (apobec3). Chemokines CXCL10 and CXCL11 were upregulated, whereas CXCL5 was downregulated. Cytokines interleukin-15 (IL-15) and IL-18 were also significantly induced, whereas IL-1alpha and IL-1beta were downregulated. Most other interleukins were not affected. The results of the microarrays were confirmed by kinetic real-time PCR. These data indicate that IFN treatment causes upregulation of genes associated with the stress response, apoptosis, and signaling, and an equal number of genes are downregulated, including those associated with protein synthesis, specific cytokines and chemokines and other biosynthetic functions.
机译:使用寡核苷酸微阵列,我们检查了聚乙二醇化干扰素-α2b(PEG-IFN-α)和利巴韦林处理的外周血细胞中22,000个基因的表达。利巴韦林处理对基因表达几乎没有影响,而PEG-IFN-α处理则具有显着效果,可调节约1000个基因的表达(p <0.001)。除了先前报道的被I型或II型IFN诱导的基因外,还发现许多新基因被上调,包括转录因子,例如ATF3,ATF4,备解素,补体途径的关键调节子,同源盒基因( HESX1)和RNA编辑酶(apobec3)。趋化因子CXCL10和CXCL11被上调,而CXCL5被下调。细胞因子白介素15(IL-15)和IL-18也被显着诱导,而IL-1alpha和IL-1beta被下调。其他大多数白介素未受影响。微阵列的结果通过动力学实时PCR证实。这些数据表明,干扰素治疗导致与应激反应,细胞凋亡和信号转导相关的基因上调,而同等数量的基因被下调,包括与蛋白质合成,特定细胞因子和趋化因子及其他生物合成功能相关的基因。

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