Global effect of PEG-IFN-α and ribavirin on gene expression in PBMC in vitro
Global effect of PEG-IFN-α and ribavirin on gene expression in PBMC in vitro
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DOI：
10.1089/107999004322813354
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发表时间：
2004-02-01
影响因子：
2.3
通讯作者：
Edenberg, HJ
中科院分区：
文献类型：
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作者：
Taylor, MW;Grosse, WM;Edenberg, HJ
利用寡核苷酸芯片，我们检测了聚乙二醇化干扰素-α2b(聚乙二醇化干扰素-α)和利巴韦林处理的外周血细胞中22,000个基因的表达。利巴韦林治疗对基因表达的影响很小，而聚乙二醇干扰素-α治疗有显著的效果，调节了大约1,000个基因的表达(在p<；0.001)。除了先前报道的由I型或II型IFN诱导的基因外，许多新的基因被发现上调，包括转录因子，如ATF3，ATF4，补体途径的关键调节因子，同源框基因(HESX1)和RNA编辑酶(APOBEC3)。趋化因子CXCL10和CXCL11表达上调，CXCL5表达下调。细胞因子IL-15和IL-18也被显著诱导，而IL-1α和IL-1β表达下调。其他大多数人没有受到影响。用实时荧光定量聚合酶链式反应对芯片结果进行了验证。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，同样数量的基因下调，包括与蛋白质合成、特定细胞因子和趋化因子以及其他生物合成功能相关的基因。
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-1 alpha and IL-1 beta 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.