| Project/Area Number |
15209059
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Emergency medicine
|
|---|
| Research Institution | Osaka 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)
|
|---|
| Keywords | immune 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
|
