@article{oai:nagasaki-u.repo.nii.ac.jp:00012813,
 author = {Hayashi, Hideki and Kohno, Tomoko and Yasui, Kiyoshi and Murota, Hiroyuki and Kimura, Tohru and Duncan, Gordon S and Nakashima, Tomoki and Yamamoto, Kazuo and Katayama, Ichiro and Ma, Yuhua and Chua, Koon Jiew and Suematsu, Takashi and Shimokawa, Isao and Akira, Shizuo and Kubo, Yoshinao and Mak, Tak Wah and Matsuyama, Toshifumi},
 issue = {46},
 journal = {Proceedings of the National Academy of Sciences of the United States of America},
 month = {Nov},
 note = {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., This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1116273108/-/DCSupplemental., Proceedings of the National Academy of Sciences of the United States of America, 108(46), pp.18766-18771; 2011},
 pages = {18766--18771},
 title = {Characterization of dsRNA-induced pancreatitis model reveals the regulatory role of IFN regulatory factor 2 (Irf2) in trypsinogen5 gene transcription.},
 volume = {108},
 year = {2011}
}