项目名称: 氧化低密度脂蛋白(ox-LDL)诱导的组织蛋白酶S(Cat S)高表达在树突状细胞(DCs)DCs激活中的作用研究
项目编号: No.81200202
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 医学一处
项目作者: 葛均华
作者单位: 青岛大学
项目金额: 20万元
中文摘要: 免疫炎症反应贯穿于动脉粥样硬化(AS)发病的各个环节。树突状细胞(DCs)是体内功能最强大的专职抗原递呈细胞,它能有效地摄取和递呈抗原,在免疫反应的诱导和调节中发挥关键作用。DCs和氧化低密度脂蛋白(ox-LDL)与AS的发病密切相关。前期研究中我们应用同位素标记蛋白质相对和绝对定量分析(iTRAQ)技术发现ox-LDL可使DCs内组织蛋白酶S(CatS)高表达。大量研究表明,CatS参与抗原递呈、脂质代谢、炎症反应、细胞外基质降解、斑块破裂和血管内膜形成等多个AS发病过程。本课题拟:①检测ox-LDL诱导的CatS高表达对DCs免疫功能的影响;②探讨丝裂原激活的蛋白激酶(MAPK)和核因子-κB(NF-κB)信号通路是否参与ox-LDL诱导的CatS高表达。本项目的完成将进一步明确ox-LDL诱导的CatS高表达在DCs活化中的作用,为深人理解DCs与AS发病的关系提供一个新视角。
中文关键词: 树突状细胞;组织蛋白酶 S;动脉粥样硬化;丝裂原激活的蛋白激酶;
英文摘要: Increasing evidences have demonstrated that atherosclerosis is an inflammatory disease.Dendritic cells (DCs) are highly specialized antigen-presenting cells (APCs) that play a central role in the initiation and regulation of both innate and adaptive immune responses. DCs play an important role in atherosclerosis because of their high antigen uptake capacity, processing, and their special ability to activate T cells. The relevance of dendritic cells (DCs) and oxidized low-density lipoproteins (ox-LDL) to the pathogenesis of atherosclerosis is well characterized. In our previous studies, iTRAQ was used to investigate the protein profile of immature and ox-LDL-treated DCs. The most interesting finding was that ox-LDL enhanced the expression of intracellular cathepsin S (Cat S), significantly. Accumulating evidences indicate that,throughout the development and progression of atherosclerosis, Cat S are involved in crucial pathological processes including the antigen presentation, apoptosis, lipid metabolism, inflammation, matrix remodeling, neovascularization, restenosis, neointima formation and plaque rupture. In this study we will focus on: ① Analysis the relevance of up-regulated Cat S and the immunological function changes of DCs. ② Analysis the role of mitogen-activated protein kinase (MAPK) and NF-κB in the pro
英文关键词: Dendritic cell;Cathepsin S;Atherosclerosis;Mitogen-activated protein kinase;