| Project/Area Number |
14370488
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Osaka University |
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Principal Investigator |
TANAKA Hirosi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90252676)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Hisashi Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (90127241)
SHIMAZU Takeshi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50196474)
OGURA Hiroshi Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70301265)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2004: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2002: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | sepsis / multiple organ failure / leukocyte / NF-κB / glucocorticoid receptor / G-CSF / stress response / 炎症性サイトカイン / グルココルチロイド受容体 / ステロイドレセプター / Insulin-like growth factor / DNAチップ |
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| Research Abstract |
The objective of our study is as follows. (1) To evaluate the balance between intranuclear NF-κB and GR in PMNLs from patients with sepsis or trauma. (2) To evaluate leukocyte functions after severe insult. (3) To investigate gene expression following stress responses.
(1) The expression of NF-κB and GR in PMNLs were significantly enhanced in SIRS patients. There was a strong correlation between, these two transcriptional factors. The PMNL oxidative activity was enhanced and plasma concentrations of IL-6, IL-8, IL- 10 and cortisol were also elevated in SIRS patients. The balance between expression of NF-κB and GR may control PMNL activation and inflammatory response following severe insults. (2) Severe trauma or sepsis enhanced expression of heat shock proteins (HSPs) in leukocytes during the acute phase. In leukocytes with enhanced expression of HSP, oxidative activity is increased and apoptosis is inhibited. The enhanced expression of HSPs may play a role in regulating leukocyte function in patients with sepsis. Activated leukocytes also enhance production of leukocyte microparticles with increased adhesion molecules in patients with sepsis. Activated leukocyte microparticles may play a role in the pathogenesis of endothelial activation and leukocyte-endothelium interaction in the presence of sepsis. (3) We found that Na/K ATPases may contribute to maintain the cellular environment of astrocytes subjected to hypoxia/reoxygenation. In the animal experiment, G-CSF administration attenuates zymosan-induced shock without suppression of reactive oxygen species. In addition, we found the enhanced expression of insulin-like growth factor in the group with G-CSF treatment by DNA micro-array method
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