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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) 小鼠阴道上皮在排卵后定期产生功能性白细胞介素 8 (IL-8) 同源物巨噬细胞炎症蛋白 (MIP)-2，并导致中性粒细胞浸润到阴道上皮。2) 在急性型 IgA 肾病中，尿液中 IL-8 水平升高，尿中单核细胞趋化蛋白检测不到（MCP）-1。相比之下，慢性 IgA 肾病患者尿液中 MCP-1 水平升高，但 IL-8 水平不升高。此外，新月体肾小球肾炎、肾脏中产生的MIP-1α和MCP-1分别导致新月体形成和间质病变。此外，在糖尿病肾病中，间质中的巨噬细胞对MCP-1呈阳性，尿中MCP-1水平升高。3)在肿瘤组织内的坏死区域附近检测到IL-8蛋白和mRNA，推测该区域的氧含量较低。几种类型的细胞系暴露于缺氧会激活两种转录因子NF-_kB和AP-1，并最终诱导IL-8基因转录。与亲代细胞相比，转染IL-8基因的人胃癌细胞系注射到裸鼠体内时表现出更快的肿瘤形成和增强的血管生成。此外，大多数胃癌细胞系表达IL-8受体，并且IL-8诱导部分胃癌细胞系中转移相关基因的表达。4）在肝癌细胞系中，两种不同的转录因子PEA3和AP-1被组成型激活，从而导致IL-8基因组成型转录。在感染人类丙型肝炎病毒的患者中，与慢性肝炎和肝硬化患者相比，患有肝癌的患者血清IL-8水平升高。此外，人丙型肝炎病毒非结构蛋白(NS) 5A 的转导诱导IL-8 基因转录以及IL-8 蛋白分泌。5) 在脐带血中，CD34 阳性细胞中的CCR1 表达仅限于红系祖细胞。