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The role of Il-18 In Inducing or preventing apoptosis in neutrophils during acute endotoxemia

IL-18在急性内毒素血症诱导或预防中性粒细胞凋亡中的作用

基本信息

批准号：
16591818
负责人：
KOTANI Joji
金额：
$ 2.05万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591818/
关键词：
IL-18 neutrophil bone marrow cells endotoxin popy unsaturated fatty acids mouse rat tumor necrosis factor 中心静脈栄養 TNF TNF receptor

项目摘要

1.The role of TNR receptors in bone marrow cell apoptosis during endotoxin-induced systemic inflammatory state. Apoptosis of myeloid cells in the bone marrow during endotoxemia is minimized as these cells undergo differentiation, which in turn, may be due to the attenuation of the pro-apoptotic effect of TNFR-p55 shown herein to occur with myeloid differentiation. In contrast, TNFR-p75 appears to play a minimal role in apoptosis induction in Grl(-) myeloid cells during endotoxemia. One explanation for a decrease in bone marrow cell numbers during endotoxemia may be via induction of apoptosis in immature myeloid cells.2.The role of IL-18 in bone marrow cell apoptosis during endotoxin-induced systemic inflammatory state. It has been demonstrated that IL-18 plays a anti-apoptotic role in mature and immature myeloid cells in the bone marrow during endotoxin-induced systemic inflammatory state.3.The role of IL-18 in both nitric oxide production and pancreatic damage during acute pancreatiti … More s. IL-18 appears to protect the pancreas during early caerulein-induced AP in mice, probably through induction of NO release from an iNOS source. IL-18 may be a target for new AP therapeutics.4.Establishment of the technique of total parenteral nutrition (TPN) in rats. We have developed the techniques to insert and fix the silicon tube into the jugular vein, transfuse TPN solution for three days safely without restriction in Wister rats.5.Apoptosis induction in the bone marrow cells during endotoxin-induced systemic inflammatory state in rats. We have confirmed that apoptosis is induced in both immature and mature bone marrow cells after intra-peritoneal injection of endotoxin like apoptosis induction in the bone marrow cells in mouse acute endotoxemia model.6.The influence of pretreatment with TPN with n-6 and n-3 poly unsaturated fatty acids (PUFAs) on apoptosis in bone marrow cells and peripheral neutrophils during endotoxin-induced systemic inflammatory state. The HPLC analysis revealed that three days TPN could change the cell wall components of spleen cells and red blood cells. Furthermore, we have found that pretreatment with TPN with n-3 PUFAs appears to increase apoptotic cell rate in the immature and mature bone marrow cells and peripheral neutrophils compared to TPN with n-6 PUFAs although the mechanisms have not been elucidated.7.The role of IL-18 in human neutrophils apotosis. IL-18, like LPS, inhibits PMN apoptosis by activating PI3-kinase and ERK pathways. However, PI3-kinase plays more important role(s) in IL-18-induced inhibition of apoptosis than in LPS-induced apoptosis inhibition.8.The influence of short chain fatty acids (SCFAs). Butyrate activates caspase cascade and induces apoptosis via signal transduction(s) other than GPR and MAPKs. It is most likely that butyrate modulate apoptosis via HDAC inhibition. Less

1. TNR受体在内毒素诱导的全身炎症状态下骨髓细胞凋亡中的作用内毒素血症期间骨髓中骨髓细胞的凋亡随着这些细胞经历分化而最小化，这又可能是由于本文所示的TNFR-p55的促凋亡作用随骨髓分化而发生的减弱。相反，TNFR-p75似乎在内毒素血症期间Grl（-）骨髓细胞的凋亡诱导中起最小作用。内毒素血症时骨髓细胞数量减少的一种解释可能是通过诱导未成熟骨髓细胞凋亡。2. IL-18在内毒素诱导的全身炎症状态下骨髓细胞凋亡中的作用。IL-18在急性胰腺炎时一氧化氮的产生和胰腺损伤中的作用 ...更多信息 S. IL-18似乎在早期雨蛙素诱导的小鼠AP期间保护胰腺，可能是通过诱导从iNOS源释放NO。IL-18可能成为AP治疗的新靶点。4.大鼠全肠外营养（TPN）技术的建立。我们建立了Wister大鼠颈静脉置管固定、无限制输注TPN溶液3天的安全技术。5.内毒素诱导的大鼠全身炎症状态下骨髓细胞凋亡的诱导。我们已经证实，腹腔注射内毒素后，未成熟和成熟的骨髓细胞都可以诱导凋亡，类似于小鼠急性内毒素血症模型中骨髓细胞的凋亡诱导。6.预先给予n-6和n-3多不饱和脂肪酸（PUFA）的TPN对内毒素诱导的全身炎症状态下骨髓细胞和外周血中性粒细胞凋亡的影响。HPLC分析表明，TPN 3d可改变脾细胞和红细胞的细胞壁成分。此外，我们还发现，与n-6 PUFAs相比，n-3 PUFAs预处理TPN似乎增加了未成熟和成熟骨髓细胞以及外周血中性粒细胞的凋亡率，尽管其机制尚未阐明。7. IL-18在人中性粒细胞凋亡中的作用。IL-18与LPS一样，通过激活PI 3-激酶和ERK途径抑制PMN凋亡。然而，PI 3-激酶在IL-18诱导的细胞凋亡抑制中的作用比在LPS诱导的细胞凋亡抑制中的作用更重要。8.短链脂肪酸的影响。丁酸盐通过GPR和MAPK以外的信号转导激活caspase级联并诱导细胞凋亡。丁酸盐最可能通过HDAC抑制来调节细胞凋亡。少

项目成果

期刊论文数量（34）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

イラストで学ぶクリティカルケアー基本手技とモニタリング

通过插图学习重症监护：基本程序和监测

DOI：
发表时间：
2004
期刊：
影响因子：
0
作者：
丸川征四郎;小谷穣治
通讯作者：
小谷穣治

腸管上皮細胞におけるToll-likereceptorsの役割

Toll样受体在肠上皮细胞中的作用

DOI：
发表时间：
2006
期刊：
日本外科代謝・栄養 39・4
影响因子：
0
作者：
鹿瀬陽一;加藤尚彦;小幡徹;他;小谷穣治
通讯作者：
小谷穣治

The mechanisms of organ dysfunction during severe infection.

严重感染期间器官功能障碍的机制。

DOI：
发表时间：
2005
期刊：
日本腹部救急医学会雑誌 25(5)
影响因子：
0
作者：
Joji Kotani;Jun-ichi Hirata;Masahiro Goshima;MD;PhD;Mariko Yamada;Munenori Matsudaira;Munehiko Ohya;Manabu Kirita;Kazumasa Yoshinaga;Seishiro Marukawa.
通讯作者：
Seishiro Marukawa.

Apoptosis And Bcl-2 Protein Family Expression In Neutrophils During Experimental Human Endotoxemia And Clinical

实验性人内毒素血症和临床中中性粒细胞凋亡和 Bcl-2 蛋白家族表达