REITERS SYNDROME--MECHANISM OF CHLAMYDIA PATHOGENESIS

描述(改编自申请人的摘要)：反应性 关节炎/瑞特综合征(ReA/RS)已知与感染有关 沙眼衣原体，因为该病经常被观察到 关注尿道炎的发作。来自调查员实验室的研究 已经表明，REA/RS病例的比例比预期大得多 都归因于这种有机体。他们进一步表明，衣原体 在REA/RS患者的滑膜组织中存在，即使在那些 疾病持续时间，在此期间生物体处于代谢活跃状态 地点。我们的数据显示，滑膜主要宿主细胞为持久性 衣原体感染是单核/巨噬细胞。其他研究也有 证明衣原体基因在滑膜中的表达异常 感染，主要外膜蛋白基因转录 (Omp1)严重减毒，强抗原性热休克 蛋白质基因(Hsp60)处于高水平。后一种衣原体蛋白是 这可能是ReA/RS滑膜炎症的原因。 衣原体在滑膜组织中持续存在并导致疾病的能力 由宿主-寄生虫的平衡相互作用产生，这是 目前在描绘分子动力学方面的应用 互动。在这里提出的研究中，调查人员采用了相反的方法 转录-聚合酶链式反应(RT-PCR)和其他检测方法 细菌基因产物与细胞分裂、能量代谢和 来自REA/RS的两个滑膜活检样本中的其他关键功能 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 评估细胞因子和其他促炎物质产生的方法 通过滑膜组织中的分子持续感染，再次使用材料 来自REA/RS患者和体外模型系统。在这些和其他方面 研究内容包括生化、分子遗传学和临床问题。 关于沙眼衣原体持续性滑膜感染的动力学。 这些研究的结果将提供一个重要的新理解 衣原体和宿主在维持炎性反应中的作用 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 滑膜和组织中的炎症，使用体外细胞 培养体系和反应性关节炎的动物模型。

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.