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

1)小鼠排卵后阴道上皮细胞周期性分泌白细胞介素-8（IL-8）同系物巨噬细胞炎性蛋白（MIP）-2，引起中性粒细胞浸润。2）伊加肾病急性期尿中IL-8水平升高，尿中单核细胞趋化蛋白（MCP）-1检测不到。与此相反，MCP-1，而不是IL-8水平增加，尿中慢性型伊加肾病患者。此外，新月体肾炎，MIP-1 α和MCP-1在肾脏中产生，分别负责新月体形成和间质病变。糖尿病肾病患者肾组织中巨噬细胞MCP-1表达阳性，尿MCP-1水平升高。3）肿瘤组织中坏死区附近检测到IL-8蛋白和mRNA，推测该区域氧含量较低。缺氧可激活NF-κ B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本细胞相比，在裸鼠体内的成瘤速度加快，血管生成增强。4）在肝癌细胞系中，两种不同的转录因子PEA 3和AP-1被组成性激活，导致IL-8基因的组成性转录。在感染丙型肝炎病毒的患者中，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基因的转录以及IL-8蛋白的分泌。5）在脐带血中，CCR 1在CD 34阳性细胞中的表达仅限于红系祖细胞。

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.