CYTOKINES AND FIBROGENESIS IN SCHISTOSOME EGG GRANULOMA

本研究的长期目标是：1）获得 关于精氨酸诱导的细胞/分子事件的知识， 维持虫卵肉芽肿相关的纤维化过程; 2） 将这些知识应用于组织纤维化的调节/抑制 临床血吸虫病。 建议的具体目标是：1） 成纤维细胞、肌成纤维细胞流入/增殖的原位检查， 胶原基因表达与胶原、细胞外基质沉积 寄生虫虫卵肉芽肿的内部 2)原位检测 细胞因子信息和细胞因子的产生在不同阶段的 肉芽肿性炎症 3)外源性IL-1 β，TNF α， TGF-β和PDGF在胶原、基质沉积中的严重结合 免疫缺陷小鼠 这些目标将通过使用 鸡卵肺肉芽肿模型、形态计量学和原位方法学 免疫细胞化学、cDNA杂交以及北方印迹， 以及mRNA信息的RT-PCR扩增。 为了不打扰 长期在我的实验室正在进行的研究，每年访问3个月 持续时间计划连续3年。 建议的范围 项目足够大，需要在申办者处进行3次单独访视 研究所完成计划的研究阶段。

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.