Development of membrane protein function analysis and the new suppression mediated by the tumor necrosis factor precursor and producing enzyme

• Project/Area Number: 24590949
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: JOH Takashi 名古屋市立大学, 医学(系)研究科(研究院), 教授 (30231369)
• Co-Investigator(Kenkyū-buntansha): TANIDA Satoshi 名古屋市立大学, 大学院医学研究科, 講師 (30528782)
• Co-Investigator(Renkei-kenkyūsha): HIGASHIYAMA Shigeki 愛媛大学, 大学院医学系研究科, 教授 (60202272)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: ADAM17 / ARP36-2 / TNFα / 新規治療ターゲット / 炎症性腸疾患 / TNF-α

Outline of Final Research Achievements

Colon epithelial cells, many expressed in monocyte cells I was paying attention to the ARP 36-2 seen. When IL-1β stimulates colon epithelial cell line, TNFα concentration in the culture solution in over time increased but TPA, LPS, increase was observed. On the other hand, when the monocytic cell line TPA stimulation, TNFα concentration in the culture solution is increased, IL-1β, the stimulation with TPA, increase was observed. Further, when the deletion of the ADAM17 by KB-R7785, siRNA, colon epithelial cells, IL-1β in the monocyte cell, the concentration increase due to TPA stimulation during TNFαshedding, was significantly inhibited. Furthermore, even if lacking the ARP36-2 by siRNA, similarly concentration rise due to IL-1β, TPA stimulus during TNFαshedding has been significantly suppressed. ARP36, it seemed to be made in inflammatory bowel disease novel therapeutic target to control the TNFαshedding.

Research Products

• [Journal Article] Annexin A2 regulates a disintegrin and metalloproteinase 17-mediated ectodomain shedding of pro-tumor necrosis factor-α in monocytes and colon epithelial cells. (2013)
  • Author(s): Tsukamoto H, Tanida S, Ozeki K, Ebi M, Mizoshita T, Shimura T, Mori Y, Kataoka H, Kamiya T, Fukuda S, Higashiyama S, Joh T.
  • Journal Title: Inflamm Bowel Dis. Volume: 19 Issue: 7 Pages: 1365-1373
  • DOI: 10.1097/mib.0b013e318281f43a
  • Peer Reviewed
• [Journal Article] Annexin A2 regulates a disintegrin and metalloproteinase 17-mediated ectodomain shedding of pro-tumor necrosis factor-α in monocytes and colon epithelial cells. (2013)
  • Author(s): Hironobu Tsukamoto, Satoshi Tanida, Keiji Ozeki, Shigeki Higashiyama, and Takashi Joh
  • Journal Title: Inflammatory Bowel Diseases Volume: in press
  • Peer Reviewed
• [Journal Article] 大腸上皮および単球細胞におけるamphiregulin-regulating protein(ARP) 36によるTNF-α放出制御機構 (2012)
  • Author(s): 塚本宏延、谷田諭史、尾関啓司、平田慶和、片岡洋望、城 卓志
  • Journal Title: Ulcer Research Volume: 39 Pages: 192-195
  • NAID: 10031061741
  • Peer Reviewed
• [Presentation] 大腸上皮および単球細胞におけるamphiregulin-regulating protein (ARP) 36によるTNFα放出制御機構
  • Author(s): 塚本宏延，谷田諭史，尾関啓司，溝下勤，森義徳，片岡洋望，神谷武，城 卓志
  • Organizer: JDDW
  • Place of Presentation: 神戸国際展示場（神戸市中央区）
• [Presentation] 大腸上皮および単球細胞におけるamphiregulin-regulating protein (ARP) 36によるTNFα放出制御機構
  • Author(s): 塚本宏延，谷田諭史，尾関啓司，溝下勤，城 卓志
  • Organizer: 第9回消化管の炎症を考える会
  • Place of Presentation: トップオブスクエア（東京都千代田区）
• [Remarks] 名古屋市立大学大学院医学研究科消化器・代謝内科学 研究業績
  • URL: http://www.ncu-shotai.ac/index.html
• [Patent(Industrial Property Rights)] 炎症性疾患治療薬のスクリーニング方法、並びに炎症性疾患の治療及び検査 (2012)
  • Inventor(s): 谷田諭史、城 卓志、東山繁樹、塚本宏延
  • Industrial Property Rights Holder: 谷田諭史、城 卓志、東山繁樹、塚本宏延
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-11-11