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Duodenal epithelial intercellular junction and IL-33 on the development of dyspepsia

Research Project

Project/Area Number 25460939
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionHyogo Medical University

Principal Investigator

OSHIMA TADAYUKI  兵庫医科大学, 医学部, 講師 (00381814)

Co-Investigator(Kenkyū-buntansha) FUKUI HIROKAZU  兵庫医科大学, 医学部, 講師 (60378742)
MIWA HIROTO  兵庫医科大学, 医学部, 教授 (80190833)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords機能性ディスペプシア / タイト結合 / クローディン / 非びらん性胃食道逆流症 / IL-33 / クロディン / 細胞間接着装置
Outline of Final Research Achievements

Duodenal epithelial cells expressed claudin (CLDN) 1, CLDN2, CLDN3, CLDN4, CLDN7,CLDN8, CLDN15, CLDN18, JAM-A, Nectin-1, Nectin-3, ZO-1, and ZO-3. The expression of each protein was different in FD patients and CLDN8 seemed to decrease in FD patients.
In vitro, IFNg, but not TNFa or IL-1b, significantly increased IL-33 mRNA compared with untreated cells. The combination of deoxycholic acid (DCA) and IFNg significantly up-regulated IL-33 mRNA compared with IFNg alone, and significantly induced more IL-8 and IL-6 compared with DCA or IFNg alone. DCA and IFNg-induced IL-33 precedes the up-regulation of IL-8 and IL-6. In order to investigate the function of nuclear up-regulated IL-33, the expression was suppressed with siRNA. IL-33 knockdown dampened IFNg-induced IL-8 and IL-6 production. These data suggest that nuclear IL-33 exaggerates the production of inflammatory cytokines.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (12 results)

All 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Serotonin disrupts esophageal mucosal integrity: an investigation using a stratified squamous epithelial model2016

    • Author(s)
      Liping Wu, Tadayuki Oshima, Toshihiko Tomita, Yoshio Ohda, Hirokazu Fukui, Jiro Watari, Hiroto Miwa
    • Journal Title

      Journal of Gastroenterology

      Volume: 未

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn2016

    • Author(s)
      Hiroo Sei, Tadayuki Oshima, Jing Shan, Liping Wu, Takahisa Yamasaki, Takuya Okugawa, Takashi Kondo, Toshihiko Tomita, Hirokazu Fukui, Jiro Watari, Hiroto Miwa
    • Journal Title

      PLoS One

      Volume: 11 Issue: 4 Pages: e0154234-e0154234

    • DOI

      10.1371/journal.pone.0154234

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Epithelial-derived nuclear IL-33 aggravates inflammation in the pathogenesis of reflux esophagitis.2015

    • Author(s)
      Shan J, Oshima T, Muto T, Yasuda K, Fukui H, Watari J, Nakanishi K, Miwa H.
    • Journal Title

      J Gastroenterol.

      Volume: 40 Issue: 4 Pages: 414-423

    • DOI

      10.1007/s00535-014-0988-1

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interferon gamma-induced nuclear interleukin-33 potentiates the release of esophageal epithelial derived cytokines2015

    • Author(s)
      Jing Shan, Tadayuki Oshima, Liping Wu, Hirokazu Fukui, Jiro Watari, Hiroto Miwa
    • Journal Title

      PLoS One

      Volume: 11 Issue: 3 Pages: e0151701-e0151701

    • DOI

      10.1371/journal.pone.0151701

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 胃食道逆流症における食道上皮細胞内IL-33の役割2016

    • Author(s)
      大島忠之,清 裕生,三輪洋人
    • Organizer
      第102回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル,東京
    • Year and Date
      2016-04-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] Current Issues in Functional Dyspepsia2016

    • Author(s)
      Hiroto Miwa
    • Organizer
      The 6th Asian Postgraduate Course on Neurogastroenterology & Motility
    • Place of Presentation
      Sheraton Grande Walkerhill Hotel, Seoul, Korea
    • Year and Date
      2016-04-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 酸関連・非酸関連上腹部症状発現のメカニズム2015

    • Author(s)
      大島忠之,ウ リピン,清 裕生,近藤 隆,三輪洋人
    • Organizer
      合同学術集会2015 第17回日本神経消化器病学会
    • Place of Presentation
      沖縄科学技術大学院大学,沖縄
    • Year and Date
      2015-11-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 機能性ディスペプシアにおける十二指腸粘膜の炎症細胞浸潤2015

    • Author(s)
      清 裕生,大島忠之,ウ リピン,原 謙,小川智広,山崎尊久,奥川卓也,近藤 隆,河野友彰,戸澤勝之,池原久朝,谷口友佳子,上山茂充,富田寿彦,應田義雄,福井広一,渡 二郎,三輪洋人
    • Organizer
      合同学術集会2015 第17回日本神経消化器病学会
    • Place of Presentation
      沖縄科学技術大学院大学,沖縄
    • Year and Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] 食道上皮細胞内のIL-33は胃食道逆流症の増悪に関与する2015

    • Author(s)
      大島忠之,単 晶,ウ リピン,清 裕生,原 謙,小川智広,山崎尊久,奥川卓也,河野友彰,近藤 隆,池原久朝,上山茂充,谷口友佳子,富田寿彦,應田義雄,福井広一,渡 二郎,三輪洋人
    • Organizer
      合同学術集会2015 第17回日本神経消化器病学会
    • Place of Presentation
      沖縄科学技術大学院大学,沖縄
    • Year and Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] 非びらん性食道胃逆流症におけるIL-33の発現と炎症性サイトカインの産生に関する検討2015

    • Author(s)
      清 裕生,大島忠之,L. Wu,山崎尊久,近藤 隆,河野友彰,豊島史彦,戸澤勝之,池原久朝,富田寿彦,應田義雄,福井広一,渡 二郎,三輪洋人
    • Organizer
      第57回日本消化器病学会大会(JDDW 2015)
    • Place of Presentation
      グランドプリンス新高輪,東京
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Upregulation and the regulation of esophageal epithelial-derived IL-33 in non-erosive reflux disease2015

    • Author(s)
      Hiroo Sei, Tadayuki Oshima, Jing Shan, Liping Wu, Takashi Kondo, Tomoaki Kono, Fumihiko Toyoshima, Katsuyuki Tozawa, Hisatomo Ikehara, Yoshio Ohda, Toshihiko Tomita, Hirokazu Fukui, Jiro Watari, Hiroto Miwa
    • Organizer
      Digestive Disease Week 2015
    • Place of Presentation
      Walter E. Washington Convention Center, Washington, DC
    • Year and Date
      2015-05-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 機能性ディスペプシアにおける十二指腸粘膜防御機構障害2014

    • Author(s)
      大島忠之,単 晶,三輪洋人
    • Organizer
      第88回日本消化器内視鏡学会総会(JDDW 2014)
    • Place of Presentation
      神戸国際展示場
    • Year and Date
      2014-10-24
    • Related Report
      2014 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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