Physiological importance of heme oxygenase-1 on hemopoiesis, inflammation and immunology system

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591275
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kanazawa University
• Principal Investigator: KOIZUMI Shoichi Kanazawa University, 子どものこころの発達研究センター, 特任教授 (50019973)
• Co-Investigator(Renkei-kenkyūsha): YACHIE Akihiro 金沢大学, 医学系, 教授 (40210281) ; WADA Tatzou 金沢大学, 医学系, 講師 (30313646) ; NISHIMURA Ryousei 金沢大学, 医学系, 講師 (50324116) ; SUGIMOTO Naotoshi 金沢大学, 医学系, 准教授 (80272954) ; OHTA Kunio 金沢大学, 医学系, 准教授 (00303280) ; NIIDA Yo 金沢大学, 子どものこころの発達研究センター, 特任准教授 (40293344) ; SAIKAWA Yutaka 金沢大学, 医学系, 教授 (60283107)
• Project Period (FY): 2008 – 2010
• Keywords: ヘムオキシゲナーゼ / 炎症 / 血管炎 / 内皮細胞 / ヘモグロビン

Research Abstract

Heme oxygenase-1(HO-1) is the rate-limiting enzyme that adds an oxygen molecule to the porphyrin ring of heme, thereby catalyzing to biliverdin, free iron (finally to bilirubin and ferritin, respectively) and carbon monoxide. In 1999, the first case of human HO-1 deficiency was reported by Yachie et al. at our Department of Pediatrics, Kanazawa University Hospital The male patient suffered from generalized severe inflammation since the age of 2, and died at 6 years of age. Quite recently the 2nd case was discovered and reported. Aggressive clinical and patho-physiological studies about these two cases and some experimental investigations have shown detailed clinical findings of HO-1 deficiency and revealed that the HO-1 enzyme is crucial for development and growth of human beings on hematopoiesis, immunological system and the defense mechanism against inflammation and oxidative stresses.

Research Products

• [Journal Article] Human heme oxygenase (HO)-1 deficiency presenting with hemolysis, nephritisand asplenia. (2011)
  • Author(s): Nita Radhakrishnan, Satya Prakash Yadav, Anuppam Sachdeva, Praveen K Pruthi, Sujata Sawhney, Tarun Piplani, Taizo Wada, Akihiro Yachie
  • Journal Title: J Pediatr Hematol Oncol 33(1) Pages: 74-81
  • Peer Reviewed
• [Journal Article] Dense methylation of type1 and type2 regulatory regions of the CD10 gene promoter in infant acute lymphoblastic leukemia with MLL/AF4 fusion gene. (2010)
  • Author(s): Ikawa Y, Sugimoto N, Koizumi S, Yachie A, Saikawa Y.
  • Journal Title: J Pediatric Hematology Oncology 32(1) Pages: 4-10
  • Peer Reviewed
• [Journal Article] Long-term results of Japanese Childhood Cancer and Leukemia Study Group studies 811, 841, 874 and 911 on childhood acute lymphoblastic leukemia. (2010)
  • Author(s): Tsurusawa M, Shimomura Y, Asami K, Kikuta A, Watanabe A, Horikoshi Y, Matsushita T, Kanegane H, Ohta S, Iwai A, Mugishima H, Koizumi S.
  • Journal Title: Leukemia 24 Pages: 335-344
  • Peer Reviewed
• [Journal Article] PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts. (2009)
  • Author(s): Hikata T, Takaishi H, Takito J, Hakozaki A, Furukawa M, Uchikawa S, Kimura T, Okada Y, Matsumoto M, Yoshimura A, Nishimura R, Reddy SV, Asahara H, Toyama Y.
  • Journal Title: Blood 113(10) Pages: 2202-2212
  • Peer Reviewed
• [Journal Article] Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome. (2008)
  • Author(s): Wada T, Yasui M, Toma T, Nakayama Y, Nishida M, Shimizu M, Okajima M, Kasahara Y, Koizumi S, Inoue M, Kawa K, Yachie A.
  • Journal Title: Blood 112(5) Pages: 1872-1875
  • Peer Reviewed
• [Journal Article] Lead-pipe colon revisited in chronic graft-versus-host disease. (2008)
  • Author(s): Saikawa Y, Ikawa Y, Kagaya T, Koizumi S.
  • Journal Title: J Pediatr Gastroenterol Nutr 46(5) Pages: 483
  • Peer Reviewed
• [Journal Article] Right homonymous hemianopsia following allogenic haematopoietic stem cell transplantation. (2008)
  • Author(s): Saikawa Y, Horisawa T, Mase S, Araki R, Ikawa Y, Kuroda R, Nishimura R, Koizumi S.
  • Journal Title: Eur J Haematol. 80(6) Pages: 551
  • Peer Reviewed
• [Journal Article] Human heme oxygenase-1 deficiency : A lesson on serendipity in the discovery of the novel disease. (2008)
  • Author(s): Koizumi S.
  • Journal Title: Pediatrics International 49(2) Pages: 125-132
  • Peer Reviewed
• [Journal Article] In vivo trafficking and survival of cytokine-induced killer cells resulting in minimal GVHD with retention of antitumor activity. (2008)
  • Author(s): Nishimura R, Baker J, Beilhack A, Zeiser R, Olson JA, Sega EI, Karimi M, Negrin RS.
  • Journal Title: Blood 112(6) Pages: 2563-2574
  • Peer Reviewed
• [Journal Article] Prevention of acute graft-versus-host disease by blocking T-cell entry to secondary lymphoid organs. (2008)
  • Author(s): Beilhack A, Schulz S, Baker J, Beilhack GF, Nishimura R, Baker EM, Landan G, Herman EI, Butcher EC, Contag CH, Negrin RS.
  • Journal Title: Blood 111(5) Pages: 2919-2928
  • Peer Reviewed
• [Presentation] Expansion of Liver-Infiltrating CTL Clone In Concert with the Development of Hepatitis-Associated AA. (2010)
  • Author(s): Yasuhiro Ikawa, Ryosei Nishimura, Shintaro Mase, Rie Kuroda, Raita Araki, Hideaki Maeba, Masaki Shimizu, Taizo Wada, Tomoko Toma, Shoichi Koizumi, Akihiro Yachie
  • Organizer: 53rd annual meeting of the American Society of Hematology.
  • Place of Presentation: San Diego Convention Center, USA
  • Year and Date: 2010-12-10
• [Presentation] Potent Strategy for Treatmet of Gvhd and Autoimmune-Diseased by Infusion of Donor-Typed or Even Third-Party Tolerogenic Dendritic Cells by Psoralen Plus UVA Treatment. (2010)
  • Author(s): Hideaki Maeba, Ryosei Nishimura, Rie Kuroda, Raita Araki, Shintaro Mase, Yasuhiro Ikawa, Akihiro Yachie, Shoichi Koizumi
  • Organizer: 53rd annual meeting of the American Society of Hematology.
  • Place of Presentation: San Diego Convention Center, USA
  • Year and Date: 2010-12-10
• [Presentation] Cytokine-Induced Killer Cells Facilitate Immune Reconstitution After Allogeneic BMT In Mice. (2010)
  • Author(s): Shintaro Mase, Ryosei Nishimura, Rie Kuroda, Hideaki Maeba, Kazuhito Naka, Raita Araki, Yasuhiro Ikawa , Shoichi Koizumi, Akihiro Yachie
  • Organizer: 53rd annual meeting of the American Society of Hematology.
  • Place of Presentation: San Diego Convention Center, USA
  • Year and Date: 2010-12-10
• [Presentation] Role of Il-17 Varies at Different Periods After Hematopoietic Stem Cell Transplantation : Protection From Acute Graft-Versus-Host Disease and Exacerbation of Chronic Graft-Versus-Host Disease. (2010)
  • Author(s): Rie Kuroda, Ryosei Nishimura, Katsuaki Sato, Hideaki Maeba, Kazuhito Naka, Shintaro Mase, Raita Araki, Yasuhiro Ikawa, Yoichiro Iwakura, Shoichi Koizumi, Akihiro Yachie
  • Organizer: 53rd annual meeting of the American Society of Hematology.
  • Place of Presentation: San Diego Convention Center, USA
  • Year and Date: 2010-12-10
• [Presentation] Strong Inhibition of Alloreaction by Newly Generated Tolerogenic Dendritic Cells by Psoralen Plus UVA Treatment. (2009)
  • Author(s): Maeba H, Nishimura R, Kuroda R, Araki R, Mase S, Ikawa Y, Yachie A, Koizumi S.
  • Organizer: 52nd annual meeting of the American Society of Hematology.
  • Place of Presentation: New Orleans Convention Center, USA
  • Year and Date: 2009-12-05
• [Presentation] Promoter DNA methylation of CD10 in infant acute lymphoblastic leukemia with MLL/AF4 fusion gene. (2009)
  • Author(s): Y.Ikawa, N.Sugimoto, S.Koizumi, A.Yachie, Y.Saikawa
  • Organizer: 2009 annual meeting of the American Society of Clinical Oncology
  • Place of Presentation: Orlando Convention Center, USA
  • Year and Date: 2009-05-29
• [Presentation] Dense Methylation Patterns of CD10 Promoters in CD 10-Negative Infant Acute Lymphoblastic Leukemia (ALL) with Mixed-Lineage Leukemia (MLL) Gene Rearrangements (2009)
  • Author(s): Yasuhiro Ikawa, Naotoshi Sugimoto, Shintaro Mase, Rie Kuroda, Raita Araki^1 Ryosei Nishimura, Toru Horisawa, Naoki Okada, Shoichi Koizumi, Akihiro Yachie, Yutaka Saikawa
  • Organizer: 100th annual meeting of the American Association of Cancer Research
  • Place of Presentation: Denver Convention Center, USA
  • Year and Date: 2009-04-18
• [Presentation] Donor Bone Marrow Derived IL-17 Expressing Cells Exacerbate Chronic Graft-Versus-Host Disease in a Murine Bone Marrow Transplantation (2008)
  • Author(s): Rie Kuroda, Ryosei Nishimura, Katsuaki Sato, Hideaki Maeba, Kazuhito Naka, Yo Niida, Raita Araki, Yoichiro Iwakura, Shoichi Koizumi, Akihiro Yachie
  • Organizer: 51st annual meeting of the American Society of Hematology.
  • Place of Presentation: San Francisco Convention Center, USA
  • Year and Date: 2008-12-05
• [Remarks] ホームページ等
  • URL: http://web.kanazawa-u.ac.jp/~med2
• [Remarks]
  • URL: http://kodomokokoro.w3.kanazawa-u.ac.jp/