EFFECTS OF HORMONES ON MUCOSAL IMMUNE MEDIATORS ACROSS THE MENSTRUAL CYCLE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 女性生殖道在免疫学上是独特的，因为它必须对精子、妊娠和阴道植物群具有耐受性，但也要保护宿主免受病原体的攻击。 此外，激素波动可能会改变粘膜环境。 细胞因子，趋化因子，免疫球蛋白，防御素和其他蛋白质提供了对性传播感染（STI）的防御，但也可以在感染的情况下或响应于杀微生物剂的阴道应用而被修改，这些药物正在开发中以预防HIV和其他STI。 关于内源性和外源性激素对宫颈阴道分泌物中单个因子的相对浓度的影响以及任何观察到的粘膜免疫变化的累积效应知之甚少。 拟议的研究将解决这一差距，并为正在进行的和未来的研究提供关键数据，这些研究涉及杀微生物剂对宫颈阴道分泌物中细胞因子，趋化因子或其他蛋白质和细胞群水平的影响。 我们建议测量两组18-35岁女性的免疫介质变化。一组将使用激素避孕，另一组将有规律的月经期。 将通过使用成熟的测定法检查液体的固有抗微生物活性来评估任何观察到的变化的生物学意义。 假设： 确定一组18-35岁女性在月经周期各期宫颈阴道液中细胞因子、趋化因子、防御素、分泌性白细胞蛋白酶抑制剂（SLPI）、免疫球蛋白和乳铁蛋白与口服避孕药女性相比的变异性。 确定从一组18-35岁女性月经周期各期获得的细胞刷样本中免疫细胞群的变异性，并与口服避孕药的女性进行比较。 确定月经周期或口服避孕药的女性中粘膜免疫介质的变化是否与内在抗菌活性的改变相关

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The female genital tract is immunologically unique because it must be tolerant to spermatozoa, pregnancy and vaginal flora, but also protect the host from pathogen challenge. Moreover, hormonal fluctuations may modify the mucosal environment. Cytokines, chemokines, immunoglobulins, defensins and other proteins provide a defense against sexually transmitted infections (STI), but also may be modified in the setting of infection or in response to vaginal application of microbicides, drugs in development to prevent HIV and other STI. Little is known about the impact of endogenous and exogenous hormones on the relative concentration of individual factors in cervicovaginal secretions and the cumulative effects of any observed changes on mucosal immunity. The proposed study will address this gap and provide critical data for ongoing and future studies that address the impact of microbicides on levels of cytokines, chemokines or other proteins and cell populations in cervicovaginal secretions. We propose to measure the changes in immune mediators in two groups of women, 18-35 years of age. One group will be using hormonal contraception and the other group will have regular menstrual periods. The biological significance of any observed changes will be assessed by examining the innate antimicrobial activity of the fluid using well-established assays. Hypothesis: To establish the variability in cytokines, chemokines, defensins, secretory leukocyte protease inhibitor (SLPI), immunoglobulins and lactoferrin in cervicovaginal fluids in a cohort of women 18-35 years of age at each phase of the menstrual cycle compared with women on oral contraceptives. To establish variability in immune cell population in cytobrush samples obtained from a cohort of women 18-35 years of age at each phase of the menstrual cycle compared with women on oral contraceptives . To determine if changes in mucosal immune mediators across the menstrual cycle or in women using oral contraceptives are associated with alterations in intrinsic antimicrobial activity