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Title
  • Characterization of dsRNA-induced pancreatitis model reveals the regulatory role of IFN regulatory factor 2 (Irf2) in trypsinogen5 gene transcription.
Creator

Hayashi, Hideki

NRID 1000010218589

Kohno, Tomoko

NRID 1000060284684

Yasui, Kiyoshi

NRID 1000050372777

Murota, Hiroyuki

Kimura, Tohru

Duncan, Gordon S

Nakashima, Tomoki

Yamamoto, Kazuo

NRID 1000070255123

Katayama, Ichiro

Ma, Yuhua

Chua, Koon Jiew

Suematsu, Takashi

Shimokawa, Isao

NRID 1000070187475

Akira, Shizuo

Kubo, Yoshinao

NRID 1000030273527

Mak, Tak Wah

Matsuyama, Toshifumi

NRID 1000030165922
Subject
  • Other Ca2+-binding proteins
  • Other Cathepsin B
  • Other IPS-1
  • Other TRIF
Description
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
PublisherNational Academy of Sciences
Date Issued 2011-11-15
Languageeng
NIItypejournal article
VersiontypeAM
Identifier URI http://hdl.handle.net/10069/26998
Relation
  • isIdenticalTo PMID 22042864
  • isIdenticalTo DOI https://doi.org/10.1073/pnas.1116273108
Journal
    • ISSN 0027-8424
    • Proceedings of the National Academy of Sciences of the United States of America
    108(46), 18766-18771
File
Oaidate2014-06-23T05:20:32Z