CYTOKINES AND FIBROGENESIS IN SCHISTOSOME EGG GRANULOMA

这项研究计划的长期目标是：1)获得 关于细胞因子诱导的细胞/分子事件的知识 并维持血吸虫虫卵肉芽肿相关的纤维化过程，2) 将这一知识应用于组织纤维化的调节/抑制 在临床血吸虫病中。该提案的具体目的是：1) 成纤维细胞、肌成纤维细胞流入/增殖的原位检测， 胶原基因表达与胶原蛋白、细胞外基质沉积 在进化中的寄生虫卵肉芽肿内。2)现场检测 细胞因子信息和细胞因子在不同发育阶段的产生 肉芽肿性炎症。3)外源性IL-1β、肿瘤坏死因子α、 转化生长因子-β和血小板衍生生长因子在胶原、基质重度联合沉积中的作用 免疫缺陷小鼠。这些目标将通过使用血吸虫来实现 卵肺肉芽肿模型、形态计量学和原位方法学 免疫细胞化学、cDNA杂交以及Northern印迹， RT-PCR扩增信使核糖核酸。为了不打扰你 从长远来看，我的实验室正在进行的研究，每年访问3个月 持续时间计划为连续3年。建议的范围 项目规模足够大，需要在赞助商处分别访问3次 研究所要完成研究的计划阶段。

The long term objectives of this research proposal are: 1) to gain knowledge on the cytokine-induced cellular/molecular events that initiate and maintain the schistosome egg granuloma related fibrotic process, 2) to apply this knowledge to the regulation/suppression of tissue fibrosis in clinical schistosomiasis. The specific aims of the proposal are: 1) In situ examination of fibroblast, myofibroblast influx/proliferation, collagen gene expression and collagen, extracellular matrix deposition within the evolving parasite egg granuloma. 2) In situ detection of cytokine message and cytokine production at various stages of the granulomatous inflammation. 3) The role of exogenous IL-1Beta, TNFalpha, TGF-Beta and PDGF in collagen, matrix deposition in severe combined immunodeficient mice. These goals will be achieved using the schistosome egg lung granuloma model, morphometry, and in situ methodologies of immunocytochemistry, cDNA hybridization, as well as Northern blotting, and RT-PCR amplification of mRNA message. In order not to interrupt for longer term the ongoing research in my lab, yearly visits of 3 months' duration are planned for 3 consecutive years. The scope of the proposed project is large enough to require 3 separate visits at the sponsor Institute to accomplish the planned phases of the research.