REITERS SYNDROME--MECHANISM OF CHLAMYDIA PATHOGENESIS

描述（改编自申请人的摘要）：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，因为经常观察到这种疾病 尿道炎发作后。 研究人员实验室的研究 已经证明 ReA/RS 病例的比例远高于预期 都归因于这种生物体。 他们进一步表明，衣原体 存在于 ReA/RS 患者的滑膜组织中，甚至存在于那些长期患病的患者中。 疾病持续时间，并且生物体在该时间段代谢活跃 网站。 我们的数据表明，持久性滑膜宿主细胞 衣原体感染是单核细胞/巨噬细胞。 其他研究有 证明滑膜期间衣原体基因表达异常 感染，主要外膜蛋白基因转录 (omp1) 严重减毒和强抗原热休克 蛋白质基因（hsp60）处于高水平。 后一种衣原体蛋白是 可能是 ReA/RS 滑膜炎症特征的原因。 衣原体在滑膜组织中持续存在并引起疾病的能力 宿主与寄生虫平衡相互作用的结果，这就是 本申请描述了其分子动力学 互动。 在这里提出的研究中，研究人员采用了反向 转录聚合酶链式反应 (RT-PCR) 和其他测定法来定义 与细胞分裂、能量代谢等相关的细菌基因产物 ReA/RS 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 持续感染中滑膜组织的分子，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 研究，他们解决生化、分子遗传学和临床问题 关于沙眼衣原体持续滑膜感染的动态。 这些研究的结果将为人们提供一个重要的新认识 衣原体和宿主在炎症维持中发挥的作用 关节疾病。 在未来的研究中，他们将采用 目前的研究旨在评估旨在减少细菌负荷的疗法 使用体外细胞观察滑膜和该组织中的炎症 反应性关节炎的培养系统和动物模型。

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.