Chemerin在梅毒螺旋体膜蛋白所致血管内皮细胞损伤中的作用机制研究

Syphilis is a chronic systemic, sexually transmitted disease caused by the bacterial spirochetal Treponema pallidum subsp. pallidum( T. pallidum，Tp). Most of the histopathological manifestations of syphilis appear to be caused by the inflammatory and immune responses mediated primarily by the lipid moiety of the lipoproteins. However, which cytokines in triggering inflammation have not been identified. Our previous studies showed that chemerin may play an important role in the immunopathogenesis of syphilis. In this study, we will produce recombinant T. pallidum membrane proteins (Tp92, Tpp47 and Tp0965) in E. coli. The effects of chemerin on dysfunction of the endothelial cells and related signal transduction pathways were identified by real-time PCR, lentivirus transfection, Western blot and other methods. The role of Chemerin/ ChemR23 pathway in reducing chemotactic movement of lymphocytes was further investigated by application of flow cytometry, confocal immunofluorescence and other methods. The results of our study will be useful for identifying the role of chemerin in the immunopathogenesis of T. pallidum, and may be a potential target for therapy of syphilis.

梅毒是由梅毒螺旋体( T. pallidum，Tp)感染所致的严重危害人类健康的性传播疾病。目前Tp致病机制尚未阐明，研究认为Tp膜蛋白所致炎症反应是导致免疫病理损伤的主要因素，但具体致炎因子及相关机制还不清楚。本课题组前期研究发现趋化因子Chemerin基因的高表达与Tp膜蛋白所致免疫病理损伤密切相关。本课题拟首先采用基因重组技术获得Tp膜蛋白Tp92、Tpp47和Tp0965；其次采用荧光定量PCR、Western-Blot、慢病毒包装及细胞转染等技术，研究Chemerin在Tp膜蛋白所致血管内皮细胞损伤中的作用及相关信号传导途径；最后，以巨噬细胞、树突状细胞为研究对象，采用免疫荧光共聚焦及流式细胞术等技术，研究Chemerin/ ChemR23通路在诱导淋巴细胞趋化中的分子机制。本课题为阐明Chemerin在梅毒免疫病理损伤中的作用及作为干预靶点提供理论基础。

梅毒是由梅毒螺旋体（Tp)感染所致的慢性系统性炎症传染病。Tp膜蛋白所致炎症反应是导致血管内皮细胞损伤主要因素，但具体致炎机制尚不清楚。在国家自然科学基金资助下，我们研究证实了Tp膜蛋白Tp92和Tp0965可诱导血管内皮细胞分泌趋化因子chemerin, chemerin 可以通过chemerin/CMKLR1信号途径以自分泌/旁分泌方式诱导血管内皮细胞活化，同时发现Tp0965通过MAPK 信号途径参与调节chemerin诱导的血管内皮炎症。另一方面，Tp92和Tp0965均可通过chemerin/ChemR23信号途径诱导THP-1 源性巨噬细胞的迁移，RhoA/ROCK信号途径是参与chemerin诱导的THP-1 源性巨噬细胞的迁移的主要信号途径。本研究目前已发表论著3篇，其中SCI期刊2篇，国家核心期刊1篇，已投稿待发表SCI期刊论著4篇。