論文

査読有り
2013年8月

Oral administration of pentachlorophenol induces interferon signaling mRNAs in C57BL16 male mouse liver

JOURNAL OF TOXICOLOGICAL SCIENCES
  • Jun Kanno
  • ,
  • Ken-ichi Aisaki
  • ,
  • Katsuhide Igarashi
  • ,
  • Satoshi Kitajima
  • ,
  • Nae Matsuda
  • ,
  • Koichi Morita
  • ,
  • Masaki Tsuji
  • ,
  • Noriko Moriyama
  • ,
  • Yusuke Furukawa
  • ,
  • Maki Otsuka
  • ,
  • Erika Tachihara
  • ,
  • Noriyuki Nakatsu
  • ,
  • Yukio Kodama

38
4
開始ページ
643
終了ページ
654
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.2131/jts.38.643
出版者・発行元
JAPANESE SOC TOXICOLOGICAL SCIENCES

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.

Web of Science ® 被引用回数 : 8

リンク情報
DOI
https://doi.org/10.2131/jts.38.643
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23892564
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000322933600012&DestApp=WOS_CPL

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