. The proposed studies will focus on cytokine/epithelial cell interactions and the importance of such interactions in the pathogenesis of HIV-1 infection in the intestinal tract and HIV-1 associated diarrhea. The first specific aim of the proposed studies is to define changes in cytokine production and the distribution of cytokine producing cells in the intestinal mucosa during the course of HIV-1 infection. These studies will use the complementary approaches of quantitative PCR analysis, in situ hybridization, and immunohistochemistry.
The second aim i s to characterize the regulation of expression of HIV-1 genes and the influence of cytokines on HIV-1 gene expression within intestinal epithelial cells.
The third aim of the proposed studies is to examine the effect of cytokines on epithelial cell function using epithelial cell lines as a model system. These studies will test the hypothesis that cytokines produced in the intestinal mucosa of HIV-1 infected patients can directly or indirectly alter the electrolyte transporting properties of intestinal epithelial cells, thereby resulting in diarrhea. The proposed studies will build on systems developed in the applicant's laboratory over the past two years. The investigator believes that new insights gained from these investigations should point to new approaches for the therapy and prevention of the disabling diarrheal syndromes that frequently accompany HIV-1 infection.
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