REITERS SYNDROME--MECHANISM OF CHLAMYDIA PATHOGENESIS

REITERS综合征--衣原体发病机制

• 批准号: 6171715
• 负责人: ALAN PAUL HUDSON
• 金额: $ 25.64万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6171715
• 关键词: Chlamydia trachomatis; DNA replication; Reiter's syndrome; bacterial DNA; bactericidal immunity; clinical research; cytokine; host organism interaction; human subject; immunocytochemistry; immunopathology; in situ hybridization; molecular pathology; pathologic process; polymerase chain reaction; synovial fluid; tissue /cell culture

DESCRIPTION (Adapted from the applicant's abstract): Reactive arthritis/Reiter's syndrome (ReA/RS) is known to be related to infection with Chlamydia trachomatis, since the disease has often been observed to follow episodes of urethritis. Studies from the investigator's laboratory have demonstrated that a far larger proportion of ReA/RS cases than expected are attributable to this organism. They have further shown that chlamydia are present in synovial tissues in ReA/RS patients, even in those with long disease duration, and that the organism is metabolically active at that site. Our data show that the primary synovial host cell for persistent chlamydial infection is the monocyte/macrophage. Other studies have demonstrated that chlamydial gene expression is aberrant during synovial infection, with transcription of the major outer membrane protein gene (omp1) severely attenuated and that of the strongly antigenic heat shock protein gene (hsp60) at high level. This latter chlamydial protein is probably the cause of the synovial inflammation characteristic of ReA/RS. The ability of chlamydia to persist in synovial tissue and cause disease results from a balanced host-parasite interaction, and it is the purpose of the present application to delineate the molecular dynamics of that interaction. In the studies proposed here, the investigators employ reverse transcription-polymerase chain reaction (RT-PCR) and other assays to define bacterial gene products relating to cell division, energy metabolism and other critical functions, in both synovial biopsy samples from ReA/RS patients and an in vitro tissue culture model system they have developed. Similarly, they use RT-PCR and other standard molecular and cell biological methods to assess production of cytokines and other proinflammatory molecules by synovial tissue in persistent infection, again using materials from both ReA/RS patients and the in vitro model system. In these and other studies, they address biochemical, molecular genetic, and clinical questions regarding the dynamics of persistent synovial infection with C. trachomatis. Results of these studies will provide a significant new understanding of the roles played by both chlamydia and host in the maintenance of inflammatory joint disease. In future research, they will employ results from the present studies to assess therapies designed to reduce bacterial load in the synovium and inflammation in that tissue, using both the in vitro cell culture system and an animal model of reactive arthritis.

描述（改编自申请人摘要）：反应性 已知关节炎/赖特综合征（ReA/RS）与感染有关 沙眼衣原体，因为这种疾病经常被观察到， 尿道炎发作后。 研究者实验室的研究 已经证明，ReA/RS病例的比例远高于预期， 都是这种生物造成的 他们进一步表明衣原体 存在于ReA/RS患者的滑膜组织中，即使在那些长时间 疾病持续时间，并且生物体在该时间段内代谢活跃 绝佳的价钱 我们的数据表明，持续性滑膜炎的主要滑膜宿主细胞 衣原体感染是单核细胞/巨噬细胞。 其他研究 表明在滑膜炎中衣原体基因表达是异常的， 感染，伴随主要外膜蛋白基因的转录 （omp 1）严重减毒和强抗原性热休克 蛋白基因（hsp 60）。 后一种衣原体蛋白是 可能是ReA/RS特征性滑膜炎症的原因。 衣原体在滑膜组织中持续存在并引起疾病的能力 结果从一个平衡的主机寄生虫的相互作用，它的目的是 本申请描述了其分子动力学， 互动 在这里提出的研究中，研究人员采用反向 转录-聚合酶链反应（RT-PCR）和其他测定，以确定 与细胞分裂、能量代谢和 其他关键功能，在ReA/RS的两份滑膜活检样本中 患者和他们开发的体外组织培养模型系统。 同样，他们使用RT-PCR和其他标准的分子和细胞生物学方法， 评估细胞因子和其它促炎因子产生的方法 在持续性感染中，滑膜组织中的分子， 来自ReA/RS患者和体外模型系统。 在这些及其它 研究，他们解决生物化学，分子遗传学和临床问题， 关于C.沙眼 这些研究的结果将提供一个重要的新的认识， 衣原体和宿主在维持炎症反应中的作用 关节疾病 在未来的研究中，他们将使用来自 目前的研究旨在评估旨在减少细菌负荷的治疗方法， 滑膜和炎症组织，使用体外细胞 培养体系和反应性关节炎动物模型。