Acetaminophen modulates the transcriptional response to recombinant interferon-beta.
Acetaminophen modulates the transcriptional response to recombinant interferon-beta.
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DOI：
10.1371/journal.pone.0011031
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发表时间：
2010-06-09
期刊：
影响因子：
3.7
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Farnsworth A;Flaman AS;Prasad SS;Gravel C;Williams A;Yauk CL;Li X
重组干扰素治疗可能会导致几种常见的副作用，包括发烧和注射部位疼痛。患者经常被建议根据需要使用对乙酰氨基酚或其他非处方止痛药。关于这种联合给药引起的转录变化，人们知之甚少。我们测试了服用对乙酰氨基酚是否会引起干扰素-β治疗引起的正常反应的改变。CD-1小鼠分别给予对乙酰氨基酚(AAPP)、干扰素-β(干扰素-β)或联合应用干扰素-β+APAP和肝脏，并采集血清标本进行分析。采用Agilent 22k小鼠全基因组芯片检测差异基因表达。数据分析采用了多种方法，包括基因本体论术语聚类和基因集浓缩分析。我们观察到当APAP与干扰素-β联合应用时，肝细胞的转录图谱发生了显著的变化。这些转录变化包括参与信号转导和细胞分化的基因显著上调，涉及细胞代谢、转运和IκBK/NF-κB级联反应的基因下调。此外，我们观察到几个干扰素诱导的基因，包括iFit-3，ISG-15，Oasl1，Zbp1和预测基因EG634650的表达在早期和晚期都大幅下降。与单独使用干扰素-β相比，联合使用干扰素-β和APAP后，转录反应发生了显著的变化。这些结果表明，醋氨酚的应用有可能改变干扰素-β的治疗效果。
Recombinant interferon treatment can result in several common side effects including fever and injection-site pain. Patients are often advised to use acetaminophen or other over-the-counter pain medications as needed. Little is known regarding the transcriptional changes induced by such co-administration. We tested whether the administration of acetaminophen causes a change in the response normally induced by interferon-β treatment. CD-1 mice were administered acetaminophen (APAP), interferon-β (IFN-β) or a combination of IFN-β+APAP and liver and serum samples were collected for analysis. Differential gene expression was determined using an Agilent 22 k whole mouse genome microarray. Data were analyzed by several methods including Gene Ontology term clustering and Gene Set Enrichment Analysis. We observed a significant change in the transcription profile of hepatic cells when APAP was co-administered with IFN-β. These transcriptional changes included a marked up-regulation of genes involved in signal transduction and cell differentiation and down-regulation of genes involved in cellular metabolism, trafficking and the IκBK/NF-κB cascade. Additionally, we observed a large decrease in the expression of several IFN-induced genes including Ifit-3, Isg-15, Oasl1, Zbp1 and predicted gene EG634650 at both early and late time points. A significant change in the transcriptional response was observed following co-administration of IFN-β+APAP relative to IFN-β treatment alone. These results suggest that administration of acetaminophen has the potential to modify the efficacy of IFN-β treatment.
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DOI：
10.1196/annals.1299.042
发表时间：
2003-01-01
期刊：
APOPTOSIS: FROM SIGNALING PATHWAYS TO THERAPEUTIC TOOLS
影响因子：
--
作者：
Hiscott, J;Grandvaux, N;Lin, RT
通讯作者：
Lin, RT
DOI：
10.1016/0928-0197(93)90021-v
发表时间：
1993-07-01
期刊：
Clinical and diagnostic virology
影响因子：
--
作者：
Chernesky, M;O'Neill, D;Mahony, J
通讯作者：
Mahony, J
影响因子：
3.8
作者：
Boulares, HA;Giardina, C;Cohen, SD
通讯作者：
Cohen, SD
影响因子：
1.8
作者：
Efron, Bradley
通讯作者：
Efron, Bradley
影响因子：
3.9
作者：
EVANS, LM;ITRI, LM;DZIEWANOWSKA, ZE
通讯作者：
DZIEWANOWSKA, ZE