Role of Bacterial Vaginosis in Preterm Delivery

描述（由申请人提供）：细菌性阴道病（BV）由 阴道生态系统的破坏，其特征在于 微生物群落通常占优势的乳酸菌浓度降低 而其它微生物区系增加（普雷沃氏菌属，消化链霉菌属，加德纳菌属， 动弯）。 研究表明BV与上生殖道感染有关， 不良妊娠结局，特别是早产（PTD）。细菌可以 通过产生导致PTD的可溶性因子来削弱胎膜 通过诱导促炎反应或刺激 前列腺素E2的产生。导致PTD的炎症反应也可以 通过附着和内化直接在宿主细胞中受到刺激 细菌我们的实验室已经开发了阴道的体外模型， 结合正常（NMVF）和BV相关混合培养物的联合收割机生态系统 （BVAF）细菌与永生化的宫颈和阴道上皮细胞， 共培养初步研究表明，这些是可行的模型， 研究阴道生态系统的细菌-上皮相互作用。数据从 使用NMVF和两种细胞系的研究表明， 粘附于上皮细胞，但只有乳杆菌属（La），普雷沃氏菌属（Pb）， 和肠球菌都被内化了此外，铅刺激白细胞介素-8 在共培养物中，La诱导显著的细胞凋亡。这 应用程序分为2个目的，旨在分析的作用， BV相关微生物群（BVAF）在PTD发病机制中的作用， 模型将表征对共培养的炎症反应， 比较使用NMVF和BVAF的结果。 坚持、内化和 将测定BVAF和NMVF的细胞凋亡率并进行比较。细菌 将确定共培养期间产生的因素，并与 刺激炎症反应。由于模型的新奇， 有独特的机会来确定BVAF在PTD中的作用。

DESCRIPTION (provided by applicant): Bacterial vaginosis (BV) results from a disruption of the vaginal ecosystem characterized by a complex shift in the microflora. Concentrations of the normally dominant Lactobacillus decrease while other microflora increase (Prevotella, Peptostreptococcus, Gardnerella, Mobiluncus). Studies have linked BV with upper genital tract infections and adverse pregnancy outcomes, particularly preterm delivery (PTD). Bacteria can weaken fetal membranes through production of soluble factors that lead to PTD either by induction of a proinflammatory response or stimulation of prostaglandin E2 production. An inflammatory response leading to PTD can also be stimulated in host cells directly through attachment and internalization of bacteria. Our laboratory has developed in vitro models of the vaginal ecosystem that combine mixed cultures of normal (NMVF) and BV-associated (BVAF) bacteria with immortalized cervical and vaginal epithelial cells in coculture. Preliminary studies demonstrate these are viable models for studying bacterial-epithelial interactions of the vaginal ecosystem. Data from studies using NMVF and both cell lines indicate that all microflora components adhere to the epithelial cells, but only Lactobacillus (La), Prevotella (Pb), and Enterococcus are internalized. In addition, Pb stimulated interleukin-8 production while La induced significant apoptosis in cocultures. This application is divided into 2 aims designed to analyze the role of BV-associated microflora (BVAF) in the pathogenesis of PTD using these unique models. The inflammatory response to coculture will be characterized, comparing findings using NMVF and BVAF. Adherence, internalization, and apoptosis rates will be determined for BVAF and NMVF and compared. Bacterial factors produced during coculture will be determined and correlated with stimulation of an inflammatory response. Due to the novelty of the models, we have the unique opportunity to determine the role of BVAF in PTD.