Inspection of receptor-Ig protein heterodimer for inhibition of its ligand

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591185
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Niigata University
• Principal Investigator: HANAWA Haruo Niigata University, 医歯学系, 講師 (40282983)
• Co-Investigator(Kenkyū-buntansha): 小玉 誠 新潟大学, 医歯学系, 准教授 (10242447)
• Project Period (FY): 2008 – 2010
• Keywords: 臨床免疫学 / 生物学的製剤 / 遺伝子治療

Research Abstract

Interleukin (IL)-1 inhibitor may be a candidate anti-inflammatory drug. We examined the effect of a heterodimer of IL-1 receptor accessory protein (Acp)-immunoglobulin (Ig) and IL-1R type II (IL1R2)-Ig named AcP-Ig/IL1R2-Ig heterodimer, and compared its effects with other IL-1 inhibitors reported previously. Our results demonstrated that the AcP-Ig/IL1R2-Ig heterodimer (rat, IC50=1.95 pM ; human, IC50=0.14 pM) inhibited IL-1 response to a greater extent than IL1RA (rat, IC50=1,935 pM), Acp-IL1R type I (IL1R1)-Ig homodimer (rat, IC50=73.7 pM ; human, IC50=4.48 pM) and Acp-IL1R2-Ig homodimer (rat IC50=72.8 pM) and strongly inhibited responses of both IL-1α and IL-1β.

Research Products

• [Journal Article] Free heme is a danger signal inducing expression of proinflammatory proteins in cultured cells derived from normal rat hearts. (2011)
  • Author(s): Hao K, Hanawa H, Ding L, Ota Y, Yoshida K, Toba K, Ogura M, Ito H, Kodama M, Aizawa Y
  • Journal Title: Mol Immunol 48 Pages: 1191-1202
  • Peer Reviewed
• [Journal Article] Expression of the peptide hormone hepcidin increases in cardiomyocytes under myocarditis and myocardial infarction. (2010)
  • Author(s): Isoda M, Hanawa H, Watanabe R, Yoshida T, Toba K, Yoshida K, Kojima M, Otaki K, Hao K, Ding L, Tanaka K, Takayama T, Kato K, Okura Y, Kodama M, Ota Y, Hayashi J, Aizawa Y
  • Journal Title: J Nutr Biochem 21 Pages: 749-756
  • Peer Reviewed
• [Journal Article] Lipocalin-2/neutrophil gelatinase-B associated lipocalin is strongly induced in hearts of rats with autoimmune myocarditis and in human myocarditis. (2010)
  • Author(s): Ding L, Hanawa H, Ota Y, Hasegawa G, Hao K, Asami F, Watanabe R, Yoshida T, Toba K, Yoshida K, Ogura M, Kodama M, Aizawa Y
  • Journal Title: Circ J 74 Pages: 523-530
  • Peer Reviewed
• [Journal Article] IL-1 Receptor Accessory Protein-Ig/IL-1 Receptor Type II-Ig Heterodimer Inhibits IL-1 Response More Strongly than Other IL-1 Blocking Biopharmaceutical Agents.
  • Author(s): Hanawa H, Ota Y, Ding L, Chang H, Yoshida K, Otaki K, Hao K, Kasahara S, Kodama M, Nakazawa M, Aizawa Y
  • Journal Title: J Clin Immunol (in press)
  • Peer Reviewed
• [Presentation] Aizawa Cytokine induced gene expression in cardiomyocytes can be identified by quantitative RT-PCR analysis in multiple samples from myocarditis hearts (2010)
  • Author(s): Haruo Hanawa, Kazuhisa Hao, Makoto Kodama, Yoshifusa.
  • Organizer: 第14回日本心不全学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-10-08
• [Presentation] Autoimmune myocarditis and its mechanism (2010)
  • Author(s): Haruo Hanawa, Tsuyoshi Yoshida, Rituo Wantanabe, Kazuhisa Hao, Limin Ding, Makoto Kodama, Yoshifusa Aizawa
  • Organizer: XXth World Congress of ISHR
  • Place of Presentation: 京都
  • Year and Date: 2010-03-30
• [Presentation] Free heme strongly induces expression of proinflammatory proteins in cultured cells derived from normal rat hearts (2010)
  • Author(s): Kazuhisa Hao, Haruo Hanawa, Limin Ding, ken Toba, Rituo Watanabe, Tsuyoshi Yoshida, Makoto Kodama, Yoshifusa Aizawa
  • Organizer: 第74回日本循環器学会総会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-07
• [Presentation] Crosstalk between component cells in rat autoimmune myocarditis(EAM)with cytokine/chemokine (2008)
  • Author(s): Hanawa H, Watanabe R, Yoshida T, Otaki K, Hao K, Ding L, Kodama M, Aizawa Y
  • Organizer: The 25th annual meeting of ISHR
  • Place of Presentation: 横浜
  • Year and Date: 2008-12-06
• [Remarks] ホームページ等
• [Patent(Industrial Property Rights)] 生物学的製剤 (2008)
  • Inventor(s): 塙晴雄
  • Industrial Property Rights Holder: 国立大学法人新潟大学
  • Industrial Property Number: 特許,特許PCT/JP2008/051457
  • Filing Date: 2008-01-30
  • Overseas