Studies on regulatory mechanisms of LPS signal transductions in human cells.

人体细胞LPS信号转导调控机制研究。

基本信息

批准号：
09670295
负责人：
MATSUURA Motohiro
金额：
$ 1.92万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670295/
关键词：
Endotoxin Lipopolysaccharide LPS Lipid A TNF IL-6 Human macrophages リボ多糖リポ多糖(LPS)TNF-α

项目摘要

The lipid A portion of bacterial LPS plays a central role in the production of endotoxic mediators. Different responses between human and murine macrophages to lipid A-like structures have been indicated. We investigated a series of structurally related monosaccharide lipid A analogues for their potency to activate human macrophage U937 cells and peripheral blood mononuclear cells for production of TNF-alpha and IL-6 compared with that of murine macrophage RAW264.7 cells. As the results, it was reveal that the structure of lipid A analogues recognized as LPS agonist by human cells comprises D-glucosamine, phosphoryl groups and acyl groups with defined carbon chain lengths of C14 and C12 in a ratio proportional to 1 : 1 : 3 ; these constituents are common to monosaccharide and disaccharide molecules and the elements necessary for recognition are more strict than those required by murine cells. In contrast, broad lipid A-like structures, which are recognized by the murine cells as LPS agonist and antagonist, are recognized as being LPS antagonist by human cells. It is now an important subject in LPS studies to find and characterize a putative LPS-receptor which transduces LPS-signals into cells. It is proposed that the protein recognizes lipid A-like structures in a productive or nonproductive manner for signal transduction and that the difference in this protein between animal species causes species specificity in the response of the cells to lipid A-like structures. In the present study, such a protein can be assumed to play a role as the target molecule for lipid A analogues to transduce their signals as LPS agonist or antagonist. Based on the information obtained in this study, further application of monosaccharide lipid A analogues as well as disaccharide analogues is promising in the search for valuable new information to elucidate of such problems.

脂质一部分细菌LP在内毒素介质的产生中起着核心作用。已经指出了人与鼠巨噬细胞对脂质A样结构的不同反应。我们研究了一系列与结构相关的单糖脂质A类似物，以激活人类巨噬细胞U937细胞和外周血单核细胞，以生产TNF-Alpha和IL-6的产生，与鼠类巨噬细胞Raw264.7细胞相比。结果是，据揭示了人类细胞识别为LPS激动剂的脂质A类似物的结构包括D-葡萄糖胺，磷酸基团和具有定义的碳链长度C14和C12的酰基基团，其比例与1：1：3成比例的比例；这些成分是单糖和二糖分子共有的，而识别所需的元素比鼠细胞所要求的要严格。相比之下，被鼠类细胞被认为是LPS激动剂和拮抗剂的宽脂质A样结构被人类细胞识别为LPS拮抗剂。现在，在LPS研究中，它是一个重要的主题，可以找到并表征推定的LPS受体，该LPS受体将LPS信号转导到细胞中。有人提出，该蛋白质以生产性或非生产性方式识别脂质A样结构，以进行信号转导，并且该蛋白质之间的动物物种之间的差异在细胞对脂质A样结构的响应中引起物种特异性。在本研究中，可以假定这种蛋白质是脂质A类似物的靶分子，以转导其信号为LPS激动剂或拮抗剂。根据本研究获得的信息，单糖脂质A类似物以及二糖类似物的进一步应用有望在寻找有价值的新信息以阐明此类问题时。