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.
