Anderson, DeborahAndry, ChristopherSingh, Subha2018-09-172018-09-172018https://hdl.handle.net/2144/31286Studies using cell lines indicate that human semen induces inflammatory changes in vaginal epithelial cell cultures, which may promote HIV transmission. Since the normal human vagina is differentiated into multiple cell layers, we conducted a study to determine the effect of semen on EpiVaginal™, a 3-D organotypic differentiated vaginal tissue model. We measured the upregulation of inflammatory cytokines by Luminex assay and microarray technology, and tissue integrity by histology and transepithelial electrical resistance (TEER) assessments. We used three multilayered differentiated EpiVaginal™ models: VEC-FT, which contained both epithelium and fibroblast layers; VEC-PT, which is comprised of differentiated epithelium only, and VLC, which has a normal epithelium in addition of fibroblasts and Langerhans cells. We hypothesized that semen is not toxic to the EpiVaginalTM tissue, which is morphologically similar to native vaginal mucosa, and does not induce a proinflammatory response. We found that semen and/or seminal plasma did not induce the expression of proinflammatory cytokines, but did significantly upregulate the expression of MCP-1, a chemokine that can attract HIV target cells such as CD4+ T cells and macrophages. We believe this research closes an important gap in understanding the impact of semen on vaginal epithelium cells by showing that semen does not have a broad proinflammatory effect on intact fully differentiated human vaginal tissues, but may induce the expression of MCP-1.en-USImmunologyThesis/Dissertation2018-07-24