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

• Project/Area Number: 25460939
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hyogo 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: ¥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.

Research Products

• [Journal Article] Serotonin disrupts esophageal mucosal integrity: an investigation using a stratified squamous epithelial model (2016)
  • Author(s): Liping Wu, Tadayuki Oshima, Toshihiko Tomita, Yoshio Ohda, Hirokazu Fukui, Jiro Watari, Hiroto Miwa
  • Journal Title: Journal of Gastroenterology Volume: 未
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn (2016)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Interferon gamma-induced nuclear interleukin-33 potentiates the release of esophageal epithelial derived cytokines (2015)
  • 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
  • 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
• [Presentation] Current Issues in Functional Dyspepsia (2016)
  • 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
  • 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
  • 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
• [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
• [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
• [Presentation] Upregulation and the regulation of esophageal epithelial-derived IL-33 in non-erosive reflux disease (2015)
  • 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
  • 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