EFFECTS OF HORMONES ON MUCOSAL IMMUNE MEDIATORS ACROSS THE MENSTRUAL CYCLE

激素对整个月经周期粘膜免疫介质的影响

基本信息

批准号：
7718170
负责人：
MARLA J KELLER
金额：
$ 17.93万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-03-01 至 2009-02-28
项目状态：
已结题

项目摘要

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

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此，可以在其他清晰的条目中表示。列出的机构是对于中心，这不一定是调查员的机构。女性生殖道在免疫学上是独一无二的，因为它必须容忍精子，妊娠和阴道菌群，但也可以保护宿主免受病原体挑战。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针对性传播感染（STI）（STI）的防御，但在感染的情况下也可能会改变，或者是对阴道施用微生物，发育中的药物的反应，以防止HIV和其他STI。关于内源性和外源激素对宫颈阴道分泌中个体因素相对浓度的影响以及任何观察到的变化对粘膜免疫的影响的影响知之甚少。拟议的研究将解决这一差距，并为正在进行的研究和未来的研究提供关键数据，以解决杀菌剂对宫颈阴道分泌中细胞因子，趋化因子或其他蛋白质和细胞群体水平的影响。我们建议衡量两组妇女（18-35岁）的免疫介体的变化。一组将使用荷尔蒙避孕，另一组将具有常规的月经期。任何观察到的变化的生物学意义将通过使用完善的测定法检查液体的先天抗菌活性来评估。假设：为了建立细胞因子，趋化因子，防御素，分泌白细胞蛋白酶抑制剂（SLPI），与口腔避孕药的女性相比，在月经周期的每个阶段的女性中，在18-35岁的女性中，女性18-35岁的女性中宫颈阴道液中的免疫球蛋白和乳糖铁蛋白。与口服避孕药的女性相比，在月经周期的每个阶段，从18-35岁的女性中获得的细胞液样品中的免疫细胞种群变异性。确定月经周期中粘膜免疫介质的变化还是使用口服避孕药的女性是否与内在抗菌活性的改变有关