Analysis of the mechanism of apperance of the autocrine motility factor in rheumatoid arthritis

自分泌运动因子在类风湿关节炎中的作用机制分析

• 批准号: 12671394
• 负责人: TAKEUCHI Kimihiko
• 金额: $ 1.09万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671394/
• 关键词: rheumatoid arthritis; AMF; PHI; FDG-PET; glycolysis; synovial fluid; gp78; anti-gp78; 滑膜; 血清; Gc-4 PF細胞; 白血球

The autocrine motility factor (AMF) which tumor secreted as a cytokine stimulates cell migration in vivo and metastasis in vitro. We identified cell motile activity not only in synovial fluid but also in serum of patients with rheumatoid arthritis (RA). Because the biochemical features of this activity were same as that of AMF, we confirm this activity to be AMF. AMF was isolated, purified, and microsequenced. And the results demonstrated that AMF is the previously cloned enzyme designed as Neuroleukin, and Phosphohexose isomerase (PHI), which has been independently implicated in cell motility, and to be a cancer progression marker. PHI catalyzes isomerization of glucose 6-phosphate to fructose 6-phosphate and specific for both sugars. Because PHI is a key enzyme of glycolytic metabolism related to accumulation of FDG within tissue, it plays an important role at a site where has an active glucose metabolism in tumor cells, or inflammatory cells. The glucose analogue, FDG, is widely used to evaluate various tumors with FDG-PET imaging. The standardized uptake value (SUV) calculated with FDG can be used as a quantitative marker of inflammation. The Lansbury index, which indicates disease activity of RA, has efficient correlation with FDG-SUV value. Serum CRP value and the number of platelet have also efficient correlation with FDG-SUV value. Histopathological examination shows that FDG-SUV value is high as the degree of neovasculization.Because synoviocytes and other inflammatory cells proliferate in rheumatoid synovial joints, AMF is considered to make a great contribution in the site of active inflammation.

肿瘤分泌的自分泌运动因子(AMF)作为细胞因子刺激细胞体内迁移和体外转移。我们不仅在类风湿性关节炎（RA）患者的滑液中而且在血清中鉴定了细胞运动活性。由于该活性的生化特征与AMF相同，因此我们确认该活性为AMF。 AMF 被分离、纯化并进行微测序。结果表明，AMF 是之前克隆的神经白介素酶和磷酸己糖异构酶 (PHI)，后者独立地与细胞运动有关，并且是癌症进展标志物。 PHI 催化 6-磷酸葡萄糖异构化为 6-磷酸果糖，并且对两种糖都有特异性。由于PHI是与组织内FDG积累相关的糖酵解代谢的关键酶，因此它在肿瘤细胞或炎症细胞中葡萄糖代谢活跃的部位发挥着重要作用。葡萄糖类似物 FDG 广泛用于通过 FDG-PET 成像评估各种肿瘤。用FDG计算的标准化摄取值(SUV)可作为炎症的定量标志物。表明 RA 疾病活动度的 Lansbury 指数与 FDG-SUV 值具有有效相关性。血清CRP值、血小板数量与FDG-SUV值也有良好的相关性。组织病理学检查显示，FDG-SUV值随新生血管形成的程度而增高。由于类风湿滑膜关节内滑膜细胞和其他炎症细胞增殖，AMF被认为在炎症活动部位做出了巨大贡献。