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Study on the mechanism of atherosclerotic lesion formation using cytokine-knockout mouse

Research Project

Project/Area Number 13470517
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionGifu University

Principal Investigator

SEISHIMA Mitsuru  Gifu University, School of Medicine, Professor, 医学部, 教授 (10171315)

Co-Investigator(Kenkyū-buntansha) FUJII Hidehiko  Gifu University, School of Medicine, Research Associate, 医学部, 助手 (50301213)
WADA Hisayasu  Gifu University, Hospital, Assistant Professor, 医学部附属病院, 講師 (10283300)
山田 泰弘  岐阜大学, 医学部, 助手 (10324295)
斉藤 邦明  岐阜大学, 医学部附属病院, 講師 (80262765)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2003: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2002: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2001: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsCytokine / Atherosclerosis / Bone marrow transplantation / Knockout mouse / Cytokines / Apoptosis
Research Abstract

1.In the study on the comparison of TNF-α^<-/-> apoE^<-/-> double KO mouse with apoE^<-/-> KO mice, the area of atherosclerotic lesion was significantly reduced in double KO mice. In addition, the expression of adhesion molecules such as ICAM-1and VCAM-1was also significantly suppressed in double KO mouse. These fidings suggest that augumented expression of adhesion molecules is, at least in part, involved in the atherosclerotic action of TNF-α.
2.The atherosclerotic lesion was significantly reduced in IFN-γ^<-/-> apoE^<-/-> double KO mice compared with apoE^<-/-> KO mice and mRNA levels of ICAM-1 and VCAM-1 were significantly decreased in double KO mice. It is suggested that mononuclear cells including monocytes are recruited to arterial wall by IL-1β, resulting in the formation of atherosclerotic lesion.
3.The atherosclerotic lesions of IFN-γ^<-/->BMT mice were larger than those of IFN-γ^<+/+>BMT mice at the aortic sinus, aortic arch and abdominal aorta. These findings show that IFN-γ produced by bone marrow-derived cells delays the progression of atherosclerosis without any effects on plasma lipids, and this suppression may be due to decreased extracellular matrix deposition.
In this study, we clarified that TNF-α and IL-1β accelerate atherosclerosis via the augumented expression of adhesion molecules in vivo study. However, IFN-y derived from bone marrow rather suppressed atherosclerosis at least in the initial stage.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Niwa T, et al.: "Interferon-γ produced by bone marrow-derived cells attenuates atherosclerotic lesion formation in LDLR-deficient mice"J Atheroscler Thromb. 11. 80-88 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kirii H, et al.: "Lack of interferon-1β decreases the sverity of atherosclerosis in apoE-deficient mice."Arterioscler Thromb Vasc Biol. 23(4). 656-660 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwasaki M, et al.: "Tumor necrosis factor-alpha from bone marrow-derived cells is not essential for the expression of adhesion molecules in lipopolysaccharide-induced nasal inflammation"Cytokine. 21(3). 129-136 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwasaki M, et al.: "TNF-α contributes to the development of allergic rhinitis in mice."J Allergy Clin Immunol. 112(1). 133-140 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 清島 満: "主要疾患における診断・治療のためのガイドラインおよび検査値「高脂血症」"臨床病理. 51. 576-580 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maekawa N., et al.: "Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α"J.Am.Coil.Cardiol.. 39(7). 1229-1235 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 清島 満 他: "臨床検査項辞典"医歯薬出版株式会社. 219-225 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Niwa T, et al.: "Interferon-γ produced by bone marrow-derived cells attenuates atherosclerotic lesion formation in LDLR-deficient mice"J Atheroscler Thromb. 11. 80-89 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kirii H, et al.: "Lack of interleukin-1β decreases the sverity of atherosclerosis in apoE-deficient mice."Arterioscler Thromb Vasc Biol. 23(4). 656-660 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwasaki M, et al.: "Tumor necrosis factor-alpha from bone marrow-derived cells is not essential for the expression of adhesion molecules in lipopolysaccharide-induced nasal inflammation."Cytokine. 21(3). 129-136 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwasaki M, et al.: "TNF-α contributes to the development of allergic rhinitis in mice."J Allergy Clin Immunol. 112(1). 133-140 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Seishima M: "Guideline for hyperlipidemia"Jpn J Clin pathol. 51. 576-580 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maekawa N, et al.: "Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α"J Am Coll Caruol. 39(7). 1229-1235 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maekawa N., et al.: "Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α"J.Am.Coll.Cardiol.. 39(7). 1229-1235 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iwasaki M., et al.: "TNF-α contributes to the development of allergic rhinitis in mice"J Allergy Clin.Immunol.. 112(1). 133-140 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iwasaki M., et al.: "Tumor necrosis factor-alpha from bone marrow-derived cells is not essential for the expression of adhesion molecules in lipopolysaccharide-induced nasal inflammation"Cytokine. 21(3). 129-136 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kirii H., et al.: "Lack of interleukin-1β decreases the severity of atherosclerosis in apoE-deficient mice"Arterioscler.Thromb.Vasc.Biol.. 23(4). 656-660 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 大橋葉津希: "金線蓮摂取の血中脂質および血糖値に与える影響について"医学と薬学. 48(5). 865-868 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 清島 満: "脂質代謝異常"臨床病理. 50(3). 219-225 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] 清島 満 他: "臨床検査項辞典"医歯薬出版株式会社. 1190 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujii H., et al.: "Immunohistochemical localization and mRNA expression of apolipoprotein A-I in rat spinal cord"J Atheroscler. Thromb. 9. 93-98 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujigaki S, et al.: "L-tryptophan-L-Kynurenine pathway metabolism accelerated by Toxoplasma gondii infection is abolished in gamma interferon-gene-deficient mice : cross-regulation between Inducible nitric oxide Synthase and indoleamine-2,3-dioxygenas"Infect. Immun.. 70. 779-786 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Maekawa N., et al.: "Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α"J. Am. Coll. Cardiol.. 39. 1229-1235 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kirii H. et al.: "Lack of interleukin-1β decreases the severity of atherosclerosis In apolipoprotein E-deficient mice"Arterioscl. Thromb. Vasc. Biol.. 23(In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morita T, et al.: "3-hydroxyanthranilic acid,an L-tryptophan metabolite,induces apoptosis in monocyte-derived cell stimulated by interferon-γ"Ann.Clin.Biochem.. 38・3. 242-251 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujigaki S, et al.: "Lipopolysaccharide induction of indoleamin 2,3-dioxygenase is mediated dominantly by an IFN-γ-independent mechanism"Eur.J.Immunol.. 31・8. 2313-2318 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Maekawa N, et al.: "Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α"J.Am.Coll.Cardiol.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] 費 華, 他: "HDL-C,LDL-C直接法の基礎的検討を基にした中国人健常者の濃度"生物試料分析. 24・2. 127-132 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 清島 満: "高脂血症の検査"日本栄養士会. 73 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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