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首页> 外文期刊>The Journal of toxicological sciences >Oral administration of pentachlorophenol induces interferon signaling mRNAs in C57BL/6 male mouse liver.
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Oral administration of pentachlorophenol induces interferon signaling mRNAs in C57BL/6 male mouse liver.

机译：五氯苯酚的口服给药可在C57BL / 6雄性小鼠肝脏中诱导干扰素信号传导mRNA。

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摘要

Pentachlorophenol (PCP) was monitored for transcriptome responses in adult mouse liver at 2, 4, 8 and 24 hr after a single oral administration at four dose levels, 0, 10, 30 and 100 mg/kg. The expression data obtained using Affymetrix GeneChip MOE430 2.0 were absolutized by the Percellome method and expressed as three dimensional (3D) surface graphs with axes of time, dose and copy numbers of mRNA per cell. We developed the programs RSort, for comprehensive screening of the 3D surface data and PercellomeExploror for cross-referencing and confirmed the significant responses by visual inspection. In the first 8 hr, approximately 100 probe sets (PSs) related to PXR/SXR and Cyp2a4 and other metabolic enzymes were induced whereas Fos and JunB were suppressed. At 24 hr, about 1,200 PSs were strongly induced. We cross-referenced the Percellome database consisting of 111 chemicals on the liver transcriptome and found that about half of the PSs belonged to the metabolic pathways including Nrf2-mediated oxidative stress response networks shared with some of the 111 chemicals. The other half of the induced genes were interferon signaling network genes (ISG) and their induction was unique to PCP. Toll like receptors and other pattern recognition receptors, interferon regulatory factors and interferon alpha itself were included but inflammatory cytokines were not induced. In summary, these data indicated that functional symptoms of PCP treatment, such as hyperthermia and profuse sweating might be mediated by the ISG rather than the previously documented mitochondrial uncoupling mechanism. PCP might become a hint for developing low molecular weight orally available interferon mimetic drugs following imiquimod and RO4948191 as agonists of toll-like receptor and interferon receptor.
机译：在以0、10、30和100 mg / kg的四种剂量水平单次口服后，在成年小鼠肝脏中监测五氯苯酚（PCP）的转录组反应。使用Affymetrix GeneChip MOE430 2.0获得的表达数据通过Percellome方法进行了绝对化处理，并表示为三维（3D）表面图，带有时间轴，每个细胞的mRNA剂量和拷贝数。我们开发了用于全面筛选3D表面数据的程序RSort和用于交叉引用的PercellomeExploror程序，并通过视觉检查确认了重要的响应。在最初的8小时内，与PXR / SXR和Cyp2a4和其他代谢酶相关的大约100个探针组（PS）被诱导，而Fos和JunB被抑制。在24小时时，强烈诱导了约1200个PS。我们交叉引用了由肝转录组上的111种化学物质组成的Percellome数据库，发现大约一半的PS属于代谢途径，包括与111种化学物质共享的Nrf2介导的氧化应激反应网络。诱导基因的另一半是干扰素信号网络基因（ISG），其诱导是PCP独有的。 Toll样受体和其他模式识别受体，干扰素调节因子和干扰素α本身也包括在内，但未诱导出炎性细胞因子。总而言之，这些数据表明PCP治疗的功能性症状（例如体温过高和大量出汗）可能是由ISG介导的，而不是先前记录的线粒体解偶联机制。 PCP可能成为继咪喹莫特和RO4948191之后作为低通量干扰素受体和干扰素受体激动剂开发低分子量口服类似物的暗示。

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