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

对严重损伤的免疫反应：通过 Toll 样受体的反应

• 批准号: 15209059
• 负责人: OGURA HIROSHI
• 金额: $ 29.12万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15209059/
• 关键词: immune response; Toll-like receptor; steroid; insults; G-CSF; intracellular cytokine; heme oxygenase-1; microparticle; toll-like receptor; heme-oxytenase-1

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

我们的研究目的如下。(1)阐明脓毒症或创伤患者对严重损伤（如Toll样受体反应性）的免疫反应。(2)为了评价严重损伤后参与免疫反应和炎症反应的细胞功能变化，我们在本研究中发现了以下结果。（1）单核细胞功能：严重SIRS患者单核细胞Toll样受体2、4和细胞内血红素氧合酶1的表达均增强。Toll样受体介导的细胞内细胞因子分泌受到抑制。用患者血清刺激时，健康志愿者单核细胞中血红素氧合酶-1的表达增强。这些结果表明，单核细胞中血红素加氧酶-1的表达增强在单核细胞失活中起作用。(2)多形核白细胞（PMNL）功能：中性粒细胞核内NF-κ B和糖皮质激素受体的表达与中性粒细胞核内NF-κ B和糖皮质激素受体的表达呈负相关。 ...更多信息 在SIRS患者中显著增强。这两个转录因子之间存在很强的相关性。NF-κ B和糖皮质激素受体表达的平衡可能调节严重损伤后PMNL的活化和炎症反应。激活的PMNLs增强了微粒的产生，增加了粘附分子对内皮的粘附。另一方面，激活的PMNLs增强了肝细胞生长因子的分泌，这支持了PMNLs在严重损伤后组织修复中的重要作用。(3)血管内皮功能：严重SIRS患者循环血液中内皮源性微粒显著增加，微粒与活化PMNL的结合增强。这些结果表明，PMNLs和内皮素之间的相互作用可能在严重损伤后的炎症反应中起重要作用。(4)γ-δ T细胞功能：严重SIRS患者循环血液中的γ-δ T细胞显著活化和减少。γ-δ T细胞可能在严重损伤后的宿主先天免疫中发挥关键作用。少

项目成果

The balance between expression of intranuclear NF-kB and glucocorticoid receptor in polymorphonuclear leukocytes in SIRS patients.

SIRS患者多形核白细胞核内NF-kB与糖皮质激素受体表达的平衡。

• 发表时间: 2005
• 期刊: J Trauma 59
• 作者: Nakamori Y;Ogura H;Koh T;Fujita K;Tanaka H;Sumi Y;Hosotsubo H;Yoshiya K;Irisawa T;Kuwagata Y;Shimazu T;Sugimoto H
• 通讯作者: Sugimoto H

Enhanced production of endothelial microparticles with increased binding To leukocytem in severe SLRS patients

严重 SLRS 患者内皮微粒的产生增强，与白细胞的结合增加

• 发表时间: 2004
• 期刊: J.Trauma 56
• 作者: T.Moriyama;T.Iida;K.Kobayashi;T.Higashi;T.Fukuoka;H.Tsumura;C.Leon;N.Suzuki;K.Inoue;C.Gachet;K.Noguchi;M.Tominaga;Nagatsuka H;Ogura H. et al.
• 通讯作者: Ogura H. et al.

Enhanced expression of intracellular heme oxygenase-1 in deactivated monocytes from patients with severs systemic inflammatory response syndrome.

严重全身炎症反应综合征患者失活单核细胞中细胞内血红素加氧酶-1 的表达增强。

• 发表时间: 2006
• 期刊: J Trauma 61
• 作者: Mohri T;Ogura H;et al.
• 通讯作者: et al.

Paradoxical cytoskeleton and microparticle formation changes in monocytes and polymorphonuclear leukocytes in severe systemic inflammatory response syndrome patients

• DOI: 10.1097/01.ta.0000096663.21402.5c
• 发表时间: 2003-12-01
• 期刊: JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
• 作者: Itakura, Y;Ogura, H;Sugimoto, H
• 通讯作者: Sugimoto, H

The balance between expression of intranuclear NF-κB and glucocorticoid receptor in polymorphonuclear leukocytes in SIRS patients.

SIRS患者多形核白细胞核内NF-κB与糖皮质激素受体表达的平衡。

• 发表时间: 2005
• 期刊: J Trauma 59
• 作者: Nakamori Y;Ogura H;Koh T;Fujita K;Tanaka H;Sumi Y;Hosotsubo H;Yoshiya K;Irisawa T;Kuwagata Y;Shimazu T;Sugimoto H
• 通讯作者: Sugimoto H