Role of Bacterial Vaginosis in Preterm Delivery

细菌性阴道病在早产中的作用

• 批准号: 6623397
• 负责人: ROBIN A ROSS
• 金额: $ 8.65万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6623397
• 关键词: Bacteroidaceae; Corynebacterium; Enterococcus; Lactobacillus; Staphylococcus epidermidis; aerobic bacteria; apoptosis; bacteria; bacteria infection mechanism; bacterial disease; bacterial proteins; cell line; cytokine; disease /disorder model; epithelium; fatty acids; flow cytometry; gas chromatography; host organism interaction; inflammation; microorganism culture; mixed tissue /cell culture; pathologic process; premature labor; prostaglandins; vaginitis

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.

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为特征，以复杂的转变为特征 菌群。正常占主导地位的乳杆菌的浓度降低 而其他菌群增加（prevotella，pepoptostopococcus，gardnerella， Mobiluncus）。 研究已将BV与上生殖道感染和 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儿膜 通过诱导促进反应或刺激 前列腺素E2生产。导致PTD的炎症反应也可以 直接通过附着和内在化在宿主细胞中刺激 细菌。我们的实验室已经开发了阴道的体外模型 结合了正常（NMVF）和BV相关的混合培养物的生态系统 （BVAF）细菌，具有永生的宫颈和阴道上皮细胞 共培养。初步研究表明，这些都是可行的模型 研究阴道生态系统的细菌上皮相互作用。来自 使用NMVF和两种细胞系的研究表明所有菌群成分 粘附于上皮细胞，但只有乳杆菌（LA），Prevotella（Pb）， 和肠球菌是内部化的。另外，PB刺激了白介素-8 LA诱导共培养物的大量凋亡。这 应用分为两个目标，旨在分析 使用这些独特的PTD发病机理中BV相关的菌群（BVAF） 型号。将表征对共培养的炎症反应， 使用NMVF和BVAF比较发现。 依从性，内在化和 将确定BVAF和NMVF的凋亡率，并比较。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。由于模型的新颖性，我们 有独特的机会来确定BVAF在PTD中的作用。