骨桥蛋白对巨噬细胞中Toll样受体触发的炎症反应的调控机制研究

项目名称： 骨桥蛋白对巨噬细胞中Toll样受体触发的炎症反应的调控机制研究

项目编号： No.81202317

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 杨海鸥

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： Toll样受体（TLRs）在机体抵抗外界病原微生物感染中发挥重要的保护作用，但TLRs信号通路的负向调控机制仍不明确。骨桥蛋白为一分泌性糖蛋白，可参与机体多种炎症性反应。我们前期研究中发现骨桥蛋白缺失（OPN-/-）小鼠在痤疮丙酸杆菌刺激下其TLR2、TLR4、TLR9、CD14、MD2、MyD88及炎症性细胞因子IL-6、TNF-α、IL-12p40、IFN-γ水平与野生型小鼠相比均显著升高，据此我们提出假设：OPN可作为负向调控因子下调TLRs介导的炎症反应。本项目拟引入OPN-/-小鼠作为研究对象，利用前期建立的原代细胞分离培养平台，运用ELISA、Western Blot及实时定量PCR方法研究OPN负向调控TLRs信号通路的分子机制。本项目的研究将进一步揭示TLRs信号通路的调节机制，对深入探索免疫识别与免疫应答调控的研究具有重要的理论意义，并为寻找免疫调节治疗的新途径指明方向。

中文关键词： Toll样受体；骨桥蛋白；免疫反应；；

英文摘要： Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns which are associated with groups of pathogens. By triggering immune response, TLRs play an important role in host defense against invading microbial pathogens. However, mechanisms underlying down-regulation of TLR-triggered inflammatory response are largely unknown. Osteopontin has been implicated in various inflammatory diseases as a glycoprotein.Our previous work has demonstrated that mRNA levels of TLR2, TLR4, TLR9, MD2, CD14 and MyD88 were significantly higher in OPN-/- mice than that in wild-type(WT) mice after treatment with P.acnes. Furthermore, the mRNA expression levels of TNF-α, IL-6, IL-12 and IFN-γ were markedly increased in the liver of OPN-/- mice compared with that of WT mice. Thereafter, we hypothesize that OPN might play as a negative regulator of TLRs-mediated inflammatory responses in macrophages. In this project, we will investigate the mechanism(s) underlying OPN-mediated signaling pathway in down-regulating TLRs response using OPN-/- mice as well as kupffer cells and peritoneal cells isolated from OPN-/- mice and WT mice. Our work will provide new insights into the function of OPN in infectious diseases、autoimmune diseases and tumor. This study will contribute to our better understandings of the regulatory mechanis

英文关键词： Toll-like receptor；osteopontin；immune response；；