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，其特征是复杂的 微生物区系。正常优势乳酸菌的浓度下降 而其他微生物区系(普氏杆菌、消化链球菌、加德纳氏菌、 Mobiluncus)。研究已经将BV与上生殖道感染和 不良妊娠结局，特别是早产。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被刺激 细菌。我们实验室已经建立了阴道的体外模型。 结合正常(NMVF)和BV相关混合培养的生态系统 (BVAF)细菌与永生化宫颈和阴道上皮细胞 共同文化。初步研究表明，这些模型是可行的 研究阴道生态系统中细菌与上皮的相互作用。数据来自 使用NMVF和两种细胞株的研究表明，所有的微生物区系成分 附着于上皮细胞，但只有乳杆菌(La)、普氏杆菌(Pb)、 和肠球菌被内化。此外，铅还能刺激白细胞介素8 La诱导共培养细胞发生明显的细胞凋亡。这 应用程序分为两个目标，旨在分析 BV相关微生物区系(BVAF)在PTD发病机制中的作用 模特们。对共培养的炎症反应将进行表征， 比较NMVF和BVAF的检查结果。坚持、内部化和 测定BVAF和NMVF的凋亡率，并进行比较。细菌 共培养过程中产生的因素将被确定并与 刺激炎症反应。由于型号的新颖性，我们 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.