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Various inflammatory cytokines and cardiovascular cells

Research Project

Project/Area Number 06670741
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionJichi Medical School

Principal Investigator

OKAWA Fujio  Jichi Medical School, Lecture, 医学部, 講師 (90260827)

Co-Investigator(Kenkyū-buntansha) IKEDA Uichi  Jichi Medical School, Assistant Professor, 医学部, 助教授 (30221063)
KUSANO Eiji  Jichi Medical School, Assistant Professor, 医学部, 助教授 (50102249)
SHIMADA Kazuyuki  Jichi Medical School, Professor, 医学部, 教授 (90145128)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
KeywordsCytokine / IL-1b / IL-6 / Nitric oxide / Eicosanoid / Leukotriene D4
Research Abstract

It is well recognized that inflammatory cytokines might be involved in the pathogenesis of various cardiovascular diseases. However, the molecular signaling mechanisms remain to be determined.
We investigated the effects of various inflammatory cytokines on the contractility of rat aorta and its molecular mechanism in cultured cardiovascular cells.
1. IL-6, not IL-2 or IL-8, is a potent inhibitor of vascular contraction, which effect is mediated through the increased cAMP synthesis. Its action is endothelium independent and mediated by the increased synthesis of prostacyclin rather than nitric oxide (NO) generation in cultured vascular smooth muscle cells (VSMC). On the other hand, IL-1b modifies its contraction by inducing gene expression of inducible nitric oxide synthase (iNOS), thereby leading to generation of NO via tyrosine kinasedependent mechanisms and this IL-b action could be also modulated by TGF-b at iNOS mRNA levels.
2. IL-1b responsive iNOS,which is an important regulator of contractile function of the heart, is present in cardiac myocytes but not in cardiac fibroblasts. Besides, cAMP upregulates IL-1b-induced iNOS expression in cardiac myocytes.
3. IL-1b induces the accumulation of eicosanoid metabolites as well as NO in VSMCs. Cyclooxygenase pathway metabolites negatively modulate IL-1b induced NO production, while the 5-lipoxygenase metabolites, such as leukotriene D4, stimulate the NO production, both at posttranscriptional levels.

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] F.Ohkawa: "Inhibitory effect of interleukin 6 on vascular smooth muscle contraction" Am.J.Physiol.266. H898-902 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Ohkawa: "Inflammatory cytokines and rat vascular tone." Clinical Experimental Pharmacology and Physiology. 20. S169-S171 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Ohkawa: "Effects of inflammatory cytokines on vascular tone." Cardiovascular Research. 30. 711-715 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] U.Ikeda,F.Ohkawa: "Cyclic AMP augments cytokine-stimulated nitric oxide synthesis in rat cardiac" J Mol Cell Cardiol. 28. 789-795 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 大川藤夫: "インターロイキン6の血管収縮抑制作用" 医薬ジャーナル. 30. 216-221 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 大川藤夫: "α1受容体血管収縮反応に及ぼすインターロイキン6の作用" 心臓. 26(Suppl 4). 9-14 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Ohkawa, U.Ikeda, K.Kawasaki, E.Kusano, M.Igarashi, K.Shimada: "Inhibitory effect of interleukin 6 on vascular smooth muscle contraction" Am.J.Physiol.266. H898-902 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Ohkawa, U.Ikeda, T.Kambe, K.Kawasaki, K.Shimada: "Inflammatory cytokines and rat vascular tone" Clinical Experimental Pharmacology and Physiology. 20. S169-S171 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Ohkawa, U.Ikeda, T.Kambe, K.Kawasaki, K.Shimada: "Effects of inflammatory cytokines on vascular tone" Cardiovascular Research. 30. 711-715 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Shinodo, U.Ikeda, F.Ohkawa, M.Takahashi, H.Funayama, Y.Kawahara, M.Yokoyama, T.Kasahara, K.Shimada: "Nitric oxide synthesis in rat cardiac myocytes and fibroblasts" Life Science. 55. 1101-1108 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Ikeda, U.Ikeda, F.Ohkawa, K.Shimada, S.Kano: "Nitric Oxide Synthesis in Rat Mesangial Cells Induced by Cytokines" Cytokine. 6. 602-607 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Shindo, U.Ikeda, F.Ohkawa, Y.Kawahara, M.Yokoyama, K.Shimada: "Nitric oxide synthesis in cardiac myocytes and fibroblasts by inflammatory cytokines" Cardiovascular Research. 29. 813-819 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] U.Ikeda, k.Yamamoto, H.Akazawa, Y.Hojo, F.Ohkawa, H.Hujikawa, H.Sekiguchi, K.Shimada: "Plasma cytokine levels in cardiac chambers of patients with mitral stenosis with congestive heart faillure" Cardiology. 87. 476-480 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] U.Ikeda, K.Yamamoto, M.Ichida, F.Ohkawa, M.Murata, O.Imura, E.Kusano, Y.Asano, K.Shimada: "Cyclic AMP augments cytokine-stimulated nitric oxide synthesis in rat cardiac myocytes" J Mol Cell Cardiol. 28. 789-795 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] U.Ikeda,K.,F.Okawa,: "Plasma cytokine levels in cardiac chambers of patients with mitral stenosis with congestive heart faillure." Cardiology. 87. 476-780 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T. Shindo: "Nitric oxide synthesis in cardiac myocytes and fibroblasts by inflammatory cytokines." Cardiovascular Research. 29. 813-819 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] F. Ohkawa: "Inflammatory cytokines and rat vascular tone." Clinical Experimental Pharmacology and Physiology. 20. S169-S171 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] F. Ohkawa: "Effects of inflammatory cytokines on vascular tone." Cardiovascular Research. 30. 711-715 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] F.Ohkawa: "Inhibitory effect of interleukin 6 on vascular smooth muscle contraction." Am.J.Physiol. 266. H898-902 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] F.Ohkawa: "Effect of various inflammatory cytokines on rat vascular tone." Clinical and Experimental Pharmacology and Physiology. in press.

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Shindo: "Nitri oxide synthesis in rat cardiac myocytes and fibroblasts." Life Science. 55. 1101-1108 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Ikeda: "Nitric Oxide Synthesis in Rat Mesangial Cells Induced by Cytokines." cytokaine. 6. 602-607 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 大川藤夫: "インターロイキン6の血管収縮抑制作用" 医薬ジャーナル. 30. 216-221 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 大川藤夫: "α1受容体血管収縮反応に及ぼすインターロインキン6の作用" 心臓. 26(Suppl4). 9-14 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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