权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Study on the regulation mechanism by endogenous bioactive substances produced by hepato-sinusoidal cells.

肝窦细胞产生的内源性生物活性物质的调控机制研究。

基本信息

批准号：
03670372
负责人：
KUROKI Tetsuo
金额：
$ 1.34万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

Hepatic sinusoidal cells are mainly constituted by Kupffer cells, hepatic sinusoidal endothelial cells, Ito cells and pit cells. In this study, we focused Kupffer cells and hepatic sinusoidal endothelial cells to analyze the role of endogenous activating substances on the regulation network in the liver.1) The production of arachidic acid metabolites and lipid metabolites by hepatic sinusoidal cells. Once rat Kupffer cells were stimulated by biological response modifiers such as lipopolysaccharide (LPS), heat-killed Propionibacterium acnes (P. acnes) and OK-432, they produced and secreted prostaglandin (PG) E2, 6-keto PGF1alpha and thromboxane (TX)B2. However, they produced PGD2 in rest state. This change was due to the induction of cyclo-oxygenase that is located on the upstream of the PG metabolic pathway. The stimulated Kupffer cells did not produce such PG metabolites unless they were inculated without Ca^<2+>, or with Ca^<2+>-chylates or calmodulin inhibitors, suggesting that their production by stimulated Kupffer cells might depend on intracellular and extracellular Ca as well as calmodulin. When Kupffer cells and hepatic sinusoidal endothelial cells were incubated with Ca ionophore, they produced platelet activating factor (PAF), a biological active lipid metabolite.2) Cytokines produced by hepatic sinusoidal cells. LPS-stimulated Kupffer cells produced interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha. This was also obsereved by stimulated hepatic sinusoidal endothelial cells. Interferon-gamma, a macrophage activating factor, led Kupffer cells to produce these cytokines, while PGE1 or PGI2 reduced such cytokine production. These results suggested the existence of the inter-and intra-regulation systems among cytokine network and arachidic acid metabolite cascade in the hepatic sinusoidal cells.

肝窦细胞主要由库普弗细胞、肝窦内皮细胞、伊藤细胞和凹陷细胞构成。本研究以库普弗细胞和肝窦内皮细胞为研究对象,分析内源性激活物质对肝脏调节网络的作用。1)肝窦细胞产生花生酸代谢物和脂质代谢物。一旦大鼠库普弗细胞受到脂多糖（LPS）、热灭活痤疮丙酸杆菌（P.acnes）和OK-432等生物反应调节剂的刺激，它们就会产生并分泌前列腺素（PG）E2、6-酮PGF1α和血栓素（TX）B2。然而，他们在静止状态下产生 PGD2。这种变化是由于位于PG代谢途径上游的环加氧酶的诱导所致。受刺激的库普弗细胞不会产生此类PG代谢物，除非它们在没有Ca 2+ 或Ca 2+ -乳酸盐或钙调蛋白抑制剂的情况下接种，这表明受刺激的库普弗细胞的产生可能取决于细胞内和细胞外Ca以及钙调蛋白。当库普弗细胞和肝窦内皮细胞与Ca离子载体一起孵育时，它们产生血小板活化因子(PAF)，这是一种生物活性脂质代谢产物。2)肝窦细胞产生的细胞因子。 LPS 刺激的 Kupffer 细胞产生白细胞介素 (IL)-1、IL-6 和肿瘤坏死因子 (TNF)-α。通过刺激肝窦内皮细胞也观察到了这一点。干扰素-γ（一种巨噬细胞激活因子）导致 Kupffer 细胞产生这些细胞因子，而 PGE1 或 PGI2 则减少此类细胞因子的产生。这些结果表明肝窦细胞细胞因子网络和花生酸代谢级联之间存在相互间和内部调节系统。