Development of assay systems for chemokines and their receptors and establishment of their diagnostic value

趋化因子及其受体测定系统的开发及其诊断价值的确立

基本信息

批准号：
10557249
负责人：
MUKAIDA Naofumi
金额：
$ 8.13万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2001
项目状态：
已结题

项目摘要

1) A functional interleukin-8 (IL-8) homologue, macrophage inflammatory protein (MIP)-2, was produced by mouse vaginal epithelium, periodically after ovulation and caused neutrophil infiltration into vaginal epithelium.2) In acute type of IgA nephropathy, urinary IL-8 levels were increased with undetectable urinary monocyte chemoattractant protein (MCP)-1. In contrast, MCP-1 but not IL-8 levels were increased in urines from chronic type of IgA nephropathy patients. Moreover, crescentic glomerulonephritis, MIP-lα and MCP-1 produced in the kidney, were responsible for crescent formation and interstitial lesions, respectively. Furthermore, in diabetic nephropathy, macrophages in interstitium were positive for MCP-1 and urinary MCP-1 levels were increased.3) IL-8 protein and mRNA were detected near necrotic areas inside tumor tissues, where oxygen content is presumed to be low. The exposure of several types of cell lines to hypoxia activated two transcription factors, NF-_kB and AP-1, and eventually induced IL-8 gene transcription. Human gastric cancer cell lines transfected with IL-8 gene exhibited faster tumor formation with enhanced angiogenesis when injected into nude mice, compared with parental cells. Moreover, most of gastric cancer cell lines expressed IL-8 receptors and IL-8 induced the expression of metastasis-related genes in some gastric cancer cell lines.4) In hepatoma cell lines, two distinct transcription factors, PEA3 and AP-1, were constitutively activated, which resulted in constitutive IL-8 gene transcription. Among patients infected with human hepatitis C virus, serum IL-8 levels were increased in patients suffering from hepatoma, when compared with chronic hepatits and liver cirrhosis patients. Moreover, the transduction of nonstructural protein (NS) 5A of human hepatitis C virus induced IL-8 gene transcription as well as IL-8 protein secretion.5) In cord blood, CCR1 expression among CD34-positive cells, was restricted to erythroid progenitor cells.

1）功能性介体8（IL-8）同源物，巨噬细胞炎性蛋白（MIP）-2是由小鼠阴道上皮产生的，在排卵后，周期性地导致急性IGA肾上腺疗法，尿素疾病，尿素性IL-8水平增加，并导致中性粒细胞中性粒细胞浸润2）（MCP）-1。相比之下，慢性IgA肾病患者的尿液中MCP-1而不是IL-8水平升高。此外，在肾脏中产生的新月肾小球肾炎，MIP-Lα和MCP-1分别负责新月形的形成和间质水平。此外，在糖尿病性肾病中，间隙中的巨噬细胞对MCP-1呈阳性，尿液MCP-1水平升高。3）IL-8蛋白和mRNA在肿瘤组织内的坏死区域附近检测到，其中氧气含量较低。几种类型的细胞系暴露于缺氧激活了两个转录因子NF-_KB和AP-1，并最终诱导IL-8基因转录。与亲本细胞相比，用IL-8基因翻译成IL-8基因的人类胃癌细胞系表现出更快的肿瘤形成，血管生成增强。此外，大多数胃癌细胞系表达IL-8受体，IL-8在某些胃癌细胞系中诱导转移相关基因的表达。4）在肝癌细胞系中，始终激活了两个不同的转录因子PEA3和AP-1，这两种不同的转录因子，PEA3和AP-1。在感染人肝炎病毒的患者中，与慢性肝和肝肝硬化患者相比，患有肝癌的患者血清IL-8水平升高。此外，人丙型肝炎病毒的非结构蛋白（NS）5a的转导诱导的IL-8基因转录以及IL-8蛋白分泌。5）在脐带血中，CCR1在CD34阳性细胞中的CCR1表达仅限于等红细胞的表达。