The role of Heme oxygenate-1 and carbon monoxide in the intestinal inflammation

• Project/Area Number: 25460959
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Tomohisa Takagi 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (70405257)
• Co-Investigator(Kenkyū-buntansha): Naito Yuji 京都府立医科大学, 医学研究科, 准教授 (00305575) ; Katada Kazuhiro 京都府立医科大学, 医学研究科, 助教 (60593910)
• Research Collaborator: Mizushima Katsura
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Heme oxygenase / 一酸化炭素 / マクロファージ / リンパ球 / Heme oxygenase-1

Outline of Final Research Achievements

In this research, we investigated the role of heme oxygenase-1 (HO-1) and carbon monoxide (CO), which is a by-product of HO-1, in intestinal inflammation. In results, we confirmed that HO-1 highly expressing macrophages expressed M2 marker, and CO regulated Th1/Th17 differentiation of lymphocytes. Thus, HO-1 and CO might regulate intestinal immune system.

Research Products

• [Journal Article] Carbon monoxide promotes gastric wound healing in mice via the protein kinase C pathway. (2016)
  • Author(s): Takagi T, Naito Y, Uchiyama K, Mizuhima K, Suzuki T, Horie R, Hirata I, Tsuboi H, Yoshikawa T.
  • Journal Title: Free Radic Res. Volume: 11 Pages: 1-19
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Multiple targets of carbon monoxide gas in the intestinal inflammation. (2016)
  • Author(s): Naito Y, Takagi T, Uchiyama K, Katada K, Yoshikawa T.
  • Journal Title: Arch Biochem Biophys. Volume: 595 Pages: 147-52
  • DOI: 10.1016/j.abb.2015.06.020
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic roles of carbon monoxide in intestinal ischemia-reperfusion injury. (2015)
  • Author(s): Katada K, Takagi T, Uchiyama K, Naito Y.
  • Journal Title: J Gastroenterol Hepatol. Volume: 30 Issue: S1 Pages: 46-52
  • DOI: 10.1111/jgh.12742
  • Peer Reviewed
• [Journal Article] The therapeutic potential of carbon monoxide for inflammatory bowel disease (2015)
  • Author(s): Takagi T, Uchiyama K, Naito Y.
  • Journal Title: Digestion Volume: 91(1) Issue: 1 Pages: 13-18
  • DOI: 10.1159/000368765
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Heme oxygenase-1 and anti-inflammatory M2 macrophages (2014)
  • Author(s): Naito, Y. Takagi, T. Higashimura, Y
  • Journal Title: Arch Biochem Biophys Volume: 564 Pages: 83-86
  • DOI: 10.1016/j.abb.2014.09.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Preventive effect of agaro-oligosaccharides on non-steroidal anti-inflammatory drug-induced small intestinal injury in mice (2014)
  • Author(s): Higashimura, Y. Naito, Y. Takagi, T. Tanimura, Y. Mizushima, K. Harusato, A. Fukui, A. Yoriki, H. Handa, O. Ohnogi, H. Yoshikawa, T.
  • Journal Title: J Gastroenterol Hepatol Volume: 29 Issue: 2 Pages: 310-317
  • DOI: 10.1111/jgh.12373
  • NAID: 110009917750
  • Peer Reviewed
• [Journal Article] BTB and CNC Homolog 1 (Bach1) Deficiency Ameliorates TNBS Colitis in Mice: Role of M2 Macrophages and Heme Oxygenase-1 (2013)
  • Author(s): Harusato, A. Naito, Y. Takagi, T. Uchiyama, K. Mizushima, K. Hirai, Y. Higashimura, Y. Katada, K. Handa, O. Ishikawa, T. Yagi, N. Kokura, S. Ichikawa, H. Muto, A. Igarashi, K. Yoshikawa, T.
  • Journal Title: Inflamm Bowel Dis Volume: 19 Issue: 4 Pages: 740-753
  • DOI: 10.1097/mib.0b013e3182802968
  • Peer Reviewed
• [Journal Article] Hemin ameliorates indomethacin-induced small intestinal injury in mice through the induction of heme oxygenase-1 (2013)
  • Author(s): Hiroyuki Yoriki
  • Journal Title: J Gastroenterol Hepatol. Volume: Apr;28(4) Issue: 4 Pages: 632-638
  • DOI: 10.1111/jgh.12074
  • Peer Reviewed
• [Journal Article] Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression. (2013)
  • Author(s): Higashimura, Y., Naito, Y., Takagi, T., Mizushima, K., Hirai, Y., Harusato, A., Ohnogi, H., Yamaji, R., Inui, H., Nakano, Y., and Yoshikawa, T.
  • Journal Title: J. Gastroenterol. Volume: 48 Issue: 8 Pages: 897-909
  • DOI: 10.1007/s00535-012-0719-4
  • NAID: 10031195116
  • Peer Reviewed
• [Presentation] Carbon monoxideを治療分子とした新規治療法の探索 (2016)
  • Author(s): 髙木智久、内山和彦、内藤裕二
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-04-21
• [Presentation] Heme oxygenase-1/Carbon monoxide系による腸管免疫制御機構の解明
  • Author(s): 髙木智久、内藤裕二、福田 亘、堅田和弘、内山和彦、半田 修、伊藤義人
  • Organizer: 第10回日本消化管学会総会学術集会
  • Place of Presentation: 福島