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タイトル
  • Characterization of dsRNA-induced pancreatitis model reveals the regulatory role of IFN regulatory factor 2 (Irf2) in trypsinogen5 gene transcription.
作成者
主題
  • other Ca2+-binding proteins
  • other Cathepsin B
  • other IPS-1
  • other TRIF
内容注記
  • Other Mice deficient for interferon regulatory factor (Irf)2 (Irf2(-/-) mice) exhibit immunological abnormalities and cannot survive lymphocytic choriomeningitis virus infection. The pancreas of these animals is highly inflamed, a phenotype replicated by treatment with poly(I:C), a synthetic double-stranded RNA. Trypsinogen5 mRNA was constitutively up-regulated about 1,000-fold in Irf2(-/-) mice compared with controls as assessed by quantitative RT-PCR. Further knockout of IFNα/β receptor 1(Ifnar1) abolished poly(I:C)-induced pancreatitis but had no effect on the constitutive up-regulation of trypsinogen5 gene, indicating crucial type I IFN signaling to elicit the inflammation. Analysis of Ifnar1(-/-) mice confirmed type I IFN-dependent transcriptional activation of dsRNA-sensing pattern recognition receptor genes MDA5, RIG-I, and TLR3, which induced poly(I:C)-dependent cell death in acinar cells in the absence of IRF2. We speculate that Trypsin5, the trypsinogen5 gene product, leaking from dead acinar cells triggers a chain reaction leading to lethal pancreatitis in Irf2(-/-) mice because it is resistant to a major endogenous trypsin inhibitor, Spink3.
  • Other identifier:Proceedings of the National Academy of Sciences of the United States of America, 108(46), pp.18766-18771; 2011
  • Other identifier:10916490
出版者 National Academy of Sciences
日付
    Issued2011-11-15
言語
  • eng
資源識別のタイプ journal article
出版タイプ AM
資源識別子 URI http://hdl.handle.net/10069/26998
関連
  • isIdenticalTo PMID 22042864
  • isIdenticalTo DOI https://doi.org/10.1073/pnas.1116273108
収録誌情報
    • ISSN 0027-8424
      • Proceedings of the National Academy of Sciences of the United States of America 108(46), 18766-18771
ファイル
コンテンツ更新日時 2014-06-23