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Immune response to severe insults: reaction through Toll-like receptors

Research Project

Project/Area Number 15209059
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionOsaka University

Principal Investigator

OGURA HIROSHI  Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (70301265)

Co-Investigator(Kenkyū-buntansha) SUGIMOTO HISASHI  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (90127241)
TANAKA HIROSHI  Osaka University, Graduate School of Medicine, Associate professor, 医学系研究科, 助教授 (90252676)
SHIMAZU TAKESHI  Osaka University, Graduate School of Medicine, Associate professor, 医学系研究科, 助教授 (50196474)
KUWAGATA YASUYUKI  Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (50273678)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥45,500,000 (Direct Cost: ¥35,000,000、Indirect Cost: ¥10,500,000)
Fiscal Year 2005: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2004: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2003: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Keywordsimmune response / Toll-like receptor / steroid / insults / G-CSF / intracellular cytokine / heme oxygenase-1 / microparticle / toll-like receptor / heme-oxytenase-1
Research Abstract

The objective of our study was as follows. (1) To clarify the immune response to severe insults (such as Toll-like receptor reactivity) in patients with sepsis or trauma. (2) To evaluate the functional changes in cells, which participate in immune reaction and inflammatory response after severe insults.
We found the following results in the present study.
(1)Monocyte functions: The expression of Toll-like receptor 2 amd 4, and intracellular heme oxygenase-1 were both enhanced in monocytes from patients with severe SIRS. The intracellular cytokine produnction through Toll-like receptors was inhibited in the patients. The heme oxygenase-1 expression in monocytes from healthy volunteers was enhanced when stimulated with the patients' serum. These results suggest that the enhanced expression of heme oxygenase-1 in monocytes plays a role in monocyte deactivation. (2) Polymorphonuclear leukocyte (PMNL) functions: The intranuclear expressions of NF-kB and glucocorticoid receptor in PMNLs were s … More ignificantly enhanced in SIRS patients. There was a strong correlation between these two transcriptional factors. The balance between expression of NF-kB and glucocorticoid receptors may regulate the PMNL activation and inflammatory response following severe insults. Activated PMNLs enhanced the production of microparticles with increased adhesion molecules to endothelium. On the other hand, activated PMNLs enhanced the secretion of hepatocyte growth factor, which supports the significant role of PMNLs in tissue repair following severe insults. (3) Vascular endothelial functions : Endothelium-derived microparticles in circulating blood were significantly increased in patients with severe SIRS, and the binding of microparticles to the activated PMNLs was enhanced. These results showed that the interaction between PMNLs and emdothelium may play an important role in inflammatory response following severe insults. (4) Gamma-delta T-cell functions : Gamma-delta T-cells were significantly activated and decreased in the circulating blood in patients with severe SIRS. Gamma-delta T-cells may play a key role in host innate immunity following severe insults. Less

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (27 results)

All 2006 2005 2004 2003 Other

All Journal Article (23 results) Publications (4 results)

  • [Journal Article] Enhanced expression of intracellular heme oxygenase-1 in deactivated monocytes from patients with severs systemic inflammatory response syndrome.2006

    • Author(s)
      Mohri T, Ogura H, et al.
    • Journal Title

      J Trauma 61

      Pages: 616-623

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Altered gut flora and environment in severs SIRS patients.2006

    • Author(s)
      Shimizu K, Ogura H, et al.
    • Journal Title

      J Trauma 60

      Pages: 126-133

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enhanced expression of intracellular heme oxygenase-1 in deactivated monocytes from patients with severe systemic inflammatory response syndrome.2006

    • Author(s)
      Mohri T, Ogura H, Koh T, Fujita K, Sumi Y, Yoshiya K, Matsushima A, Hosotsubo H, Kuwagata Y, Tanaka H, Shimazu T, Sugimoto H.
    • Journal Title

      J Trauma 61

      Pages: 616-623

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Altered gut flora and environment in severe SIRS patients.2006

    • Author(s)
      Shimizu K, Ogura H, Goto M, Kuwagata Y, Tanaka H, Shimazu T, Sugimoto H
    • Journal Title

      J Trauma 60

      Pages: 126-133

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The balance between expression of intranuclear NF-κ B and glucocorticoid receptor in polymorphonuclear leukocytes in SIRS patients.2005

    • Author(s)
      Nakamori Y, Ogura H, et al.
    • Journal Title

      J Trauma 59

      Pages: 308-315

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The balance between expression of intranuclear NF-kB and glucocorticoid receptor in polymorphonuclear leukocytes in SIRS patients.2005

    • Author(s)
      Nakamori Y, Ogura H, Koh T, Fujita K, Tanaka H, Sumi Y, Hosotsubo H, Yoshiya K, Irisawa T, Kuwagata Y, Shimazu T, Sugimoto H
    • Journal Title

      J Trauma 59

      Pages: 308-315

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The balance between expression of intranuclear NF-kB and glucocorticoid receptor in PMNL in severe SIRS patients.2005

    • Author(s)
      Nakamori Y. et al.
    • Journal Title

      J Trauma 59

      Pages: 308-315

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hepatocyte growth factor in polymorphonuclear leukocytes is increased in patients with systemic inflammatory response syndrome.2004

    • Author(s)
      Matsushima A, Ogura H, et al.
    • Journal Title

      J Trauma 56

      Pages: 259-264

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enhanced production of endothelial microparticles with increased binding to leukocytes in patients with severe systemic inflammatory response syndrome.2004

    • Author(s)
      Ogura H, Tanaka H, et al.
    • Journal Title

      J Trauma 56

      Pages: 823-831

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Early activation of γ δ T lymphocytes in patients with severe systemic inflammatory response syndrome.2004

    • Author(s)
      Matsushima A, Ogura H, et al.
    • Journal Title

      Shock 22

      Pages: 11-15

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 総説-マイクロパーティクル産生からみたsepsisの病態解明2004

    • Author(s)
      藤見 聡, 小倉 裕司 ら
    • Journal Title

      炎症・再生 24

      Pages: 18-26

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 総説-白血球制御による新たなる抗炎症治療戦略 : Granulocyte-colony stimulating factor(G-CSF)療法2004

    • Author(s)
      田中裕, 石川和男, 西野正人, 小倉裕司 ら
    • Journal Title

      炎症・再生 24

      Pages: 619-628

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hepatocyte growth factor in polymorphonuclear leukocytes is increased in patients with systemic inflammatory response syndrome.2004

    • Author(s)
      Matsushima A, Ogura H, Koh T, Fujita K, Yoshiya K, Sumi Y, Hosotsubo H, Kuwagata Y, Tanaka H, Shimazu T, Sugimoto H
    • Journal Title

      J Trauma 56

      Pages: 259-264

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enhanced production of endothelial microparticles with increased binding to leukocytes in patients with severe systemic inflammatory response syndrome.2004

    • Author(s)
      Ogura H, Tanaka H, Koh T, Fujita K, Fujimi S, Nakamori Y, Hosotsubo H, Kuwagata Y, Shimazu T, Sugimoto H
    • Journal Title

      J Trauma 56

      Pages: 823-831

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Early activation of γ δ T lymphocytes in patients with severe systemic inflammatory response syndrome.2004

    • Author(s)
      Matsushima A, Ogura H, Fujita K, Koh T, Tanaka H, Sumi Y, Yishiya K, Hosotsubo H, Kuwagata Y, Shimazu T, Sugimoto H
    • Journal Title

      Shock 22

      Pages: 11-15

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Enhanced production of endothelial microparticles with increased binding To leukocytem in severe SLRS patients2004

    • Author(s)
      Ogura H. et al.
    • Journal Title

      J.Trauma 56

      Pages: 823-831

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hepatocute growth factor in polymerphonuclear leukocyte is increased in patients with STRS.2004

    • Author(s)
      MATSUSHIMA A. et al.
    • Journal Title

      J.Trauma 56

      Pages: 259-264

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Early activation of γδ T lymphocytes in patients with severe SIRS2004

    • Author(s)
      MATSUSHIMA A. et al.
    • Journal Title

      Shock 22

      Pages: 11-15

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Paradoxical cytoskeleton and microparticle formation changes in monocytes and polymorphonuclear leukocytes in severe systemic inflammatory response syndrome patients.2003

    • Author(s)
      Sumi Y, Ogura H, et al.
    • Journal Title

      J Trauma 55

      Pages: 1125-1132

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increased production of leukocyte microparticles with enhanced expression of adhesion molecules in from activated polymorphonuclear leukocytes in severely injured patients.2003

    • Author(s)
      Fujimi S, Ogura H, et al.
    • Journal Title

      J Trauma 54

      Pages: 114-120

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Paradoxical cytoskeleton and microparticle formation changes in monocytes and polymorphonuclear leukocytes in severe systemic inflammatory response syndrome patients.2003

    • Author(s)
      Sumi Y, Ogura H, Tanaka H, Koh T, Fujita K, Fujimi S, Nakamori Y, Shimazu T, Sugimoto H
    • Journal Title

      J Trauma 55

      Pages: 1125-1132

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increased production of leukocyte microparticles with enhanced expression of adhesion molecules in from activated polymorphonuclear leukocytes in severely injured patients.2003

    • Author(s)
      Fujimi S, Ogura H, Tanaka H, Koh T, Hosotsubo Nakamori Y, Kuwagata Y, Shimazu T, Sugimoto
    • Journal Title

      J Trauma 54

      Pages: 114-120

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The balance between expression of intramuscular NF-kB and glucocortid receptor in polymorph nuclear leukocytes in SIRS patients.

    • Author(s)
      Nakamori Y. et al.
    • Journal Title

      J.Trauma (in press)

    • Related Report
      2004 Annual Research Report
  • [Publications] Sumi Y et al.: "Paradoxical cytoskeleton and microparticle formation changes in monocytes and PMNLs in severe SIRS patients"J.Trauma. 55. 1125-1132 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogura H et al.: "Microparticles in severe SIRS patients"Microcirculation Annual. 19. 77-78 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujimi S et al.: "Increased production of leukocyte microparticles with enhanced expression of adhesion molecules severely injured patients"J.Trauma. 54. 114-120 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogura H et al.: "Enhanced production of endothelial microparticles with increased binding to leukocytes in severe SIRS"J.Trauma. (in press).

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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