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Characterization of dsRNA-induced pancreatitis model reveals the regulatory role of IFN regulatory factor 2 (Irf2) in trypsinogen5 gene transcription.
http://hdl.handle.net/10069/26998
http://hdl.handle.net/10069/2699804aed2e0-ce1b-4f11-bb65-a9eeea91d620
名前 / ファイル | ライセンス | アクション |
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PNAS108_18766.pdf (1.4 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2012-01-04 | |||||
タイトル | ||||||
タイトル | Characterization of dsRNA-induced pancreatitis model reveals the regulatory role of IFN regulatory factor 2 (Irf2) in trypsinogen5 gene transcription. | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Ca2+-binding proteins | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Cathepsin B | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | IPS-1 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | TRIF | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Hayashi, Hideki
× Hayashi, Hideki× Kohno, Tomoko× Yasui, Kiyoshi× Murota, Hiroyuki× Kimura, Tohru× Duncan, Gordon S× Nakashima, Tomoki× Yamamoto, Kazuo× Katayama, Ichiro× Ma, Yuhua× Chua, Koon Jiew× Suematsu, Takashi× Shimokawa, Isao× Akira, Shizuo× Kubo, Yoshinao× Mak, Tak Wah× Matsuyama, Toshifumi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1116273108/-/DCSupplemental. | |||||
書誌情報 |
Proceedings of the National Academy of Sciences of the United States of America 巻 108, 号 46, p. 18766-18771, 発行日 2011-11-15 |
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出版者 | ||||||
出版者 | National Academy of Sciences | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 00278424 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 10916490 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA10808769 | |||||
PubMed番号 | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | PMID | |||||
関連識別子 | 22042864 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1073/pnas.1116273108 | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Proceedings of the National Academy of Sciences of the United States of America, 108(46), pp.18766-18771; 2011 |