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产生一种功能性白介素8(IL-8)类似物巨噬细胞炎性蛋白(MIP)-2，并引起中性粒细胞渗入阴道上皮。2)在急性型IgA肾病中，尿IL-8水平升高，尿单核细胞趋化蛋白(MCP)-1检测不到。相反，慢性IgA肾病患者尿液中MCP-1水平升高，而IL-8水平无明显变化。此外，新月体肾炎、肾脏产生的巨噬细胞炎性蛋白-Lα和单核细胞趋化蛋白-1分别是新月体形成和间质病变的原因。此外，在糖尿病肾病中，间质巨噬细胞MCP-1呈阳性反应，尿MCP-1水平升高。3)IL-8蛋白和mRNA在肿瘤组织内坏死区附近检测到，推测这些坏死区含氧量较低。几种类型的细胞暴露在低氧下，激活了两种转录因子--核因子-kB和AP-1，最终诱导了IL-8基因的转录。与亲代细胞相比，转IL-8基因的人胃癌细胞株在裸鼠体内的成瘤速度更快，血管生成能力更强。此外，大多数胃癌细胞株表达IL-8受体，IL-8可诱导部分胃癌细胞株转移相关基因的表达。4)在肝癌细胞系中，两个不同的转录因子PEA3和AP-1被结构性激活，导致IL-8基因的结构性转录。在人类丙型肝炎病毒感染者中，肝癌患者血清IL-8水平高于慢性肝炎和肝硬变患者。此外，转导人丙型肝炎病毒非结构蛋白(NS)5A可诱导IL-8基因转录和IL-8蛋白分泌。5)脐血中CD34阳性细胞中CCR1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.