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

1)小鼠阴道上皮在排卵后周期性产生白细胞介素-8 （IL-8）的功能性同源物巨噬细胞炎症蛋白(MIP)-2，引起中性粒细胞浸润阴道上皮。2)急性型IgA肾病患者尿IL-8水平升高，且尿单核细胞化学引诱蛋白(MCP)-1检测不到。相比之下，慢性IgA肾病患者尿液中MCP-1水平升高，但IL-8水平未升高。此外，月牙状肾小球肾炎，肾脏产生的MIP-lα和MCP-1分别是月牙状形成和间质病变的原因。此外，糖尿病肾病患者间质巨噬细胞MCP-1阳性，尿MCP-1水平升高。3)肿瘤组织内坏死区附近检测到IL-8蛋白和mRNA，推测坏死区氧含量较低。几种类型的细胞系暴露于缺氧条件下，可激活NF-_kB和AP-1两种转录因子，最终诱导IL-8基因转录。转染IL-8基因的人胃癌细胞系与亲代细胞相比，注射到裸鼠体内，肿瘤形成速度更快，血管生成能力增强。此外，大多数胃癌细胞系表达IL-8受体，IL-8可诱导部分胃癌细胞系转移相关基因的表达。4)在肝癌细胞系中，PEA3和AP-1两种不同的转录因子被组成性激活，从而导致IL-8基因的组成性转录。在丙型肝炎病毒感染者中，与慢性肝炎和肝硬化患者相比，肝癌患者血清IL-8水平升高。此外，人丙型肝炎病毒非结构蛋白（NS） 5A的转导可诱导IL-8基因的转录和IL-8蛋白的分泌。5)在脐带血中，CCR1在cd34阳性细胞中的表达仅限于红细胞祖细胞。

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.