MECHANISMS BEHIND CX2CL1-DRIVEN MONOCYTE RECRUITMENT DURING PERIODONTITIS

牙周炎期间 CX2CL1 驱动的单核细胞募集背后的机制

• 批准号: 7610702
• 负责人: Rebecca Worthylake
• 金额: $ 22.25万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610702
• 关键词: Adhesions; Biological Models; Blood Circulation; CX3CL1 gene; Cells; Chronic; Computer Retrieval of Information on Scientific Projects Database; Cultured Cells; Experimental Models; Foundations; Funding; Gingiva; Goals; Grant; Immune system; Inflammation; Institution; Leukocytes; Link; Molecular; Periodontal Diseases; Periodontitis; Process; Protein-Serine-Threonine Kinases; Recruitment Activity; Regulation; Research; Research Personnel; Research Project Grants; Research Proposals; Resources; Signal Transduction; Source; Tissues; United States National Institutes of Health; chemokine; cytokine; design; in vivo; migration; monocyte

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Periodontal disease results from chronic inflammation which is induced and maintained by the recruitment of circulating leukocytes into the gingival tissues. This research proposal is designed to investigate the mechanism by which circulating monocytes are captured by the local vasculature, the first step in the process of transmigration into gingival tissue. While many different immune system cells, chemokines, and cytokines are implicated in periodontal inflammation we choose to focus our study on CX3CL1, a chemokine associated with monocyte capture during periodontitis. Our hypothesis is that CX3CL1 promotes periodontitis by regulating the molecular migration machinery required to recruit monocyte exit from the circulation to enter the underlying gingival tissue. In Aim I. we will investigate CX3CL1 regulation of the molecular machinery needed for adhesion and transmigration. In Aim II. we will link CX3CL1 signaling to the regulation of ROCK, a serine/threonine kinase with potent effects on monocyte adhesion and transendothelial migration. The overall goal of this research project is to take advantage of an easy-to-manipulate cell culture model system to define key regulatory mechanisms in CX3CL1-driven monocyte recruitment, which will be the foundation for developing an in vivo periodontitis experimental model.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 牙周病是由慢性炎症引起的，慢性炎症是由于循环中的白细胞重新聚集到牙龈组织中而引起和维持的。这项研究计划旨在研究循环中的单核细胞被局部血管系统捕获的机制，这是向牙龈组织迁移过程的第一步。虽然许多不同的免疫系统细胞、趋化因子和细胞因子与牙周炎症有关，但我们选择将研究重点放在CX3CL1上，这是一种与牙周炎期间单核细胞捕获相关的趋化因子。我们的假设是，CX3CL1通过调节分子迁移机制来促进牙周炎，分子迁移机制需要招募单核细胞从循环中退出进入牙龈组织。在目标I中，我们将研究CX3CL1对黏附和迁移所需的分子机制的调节。在AIM II中，我们将CX3CL1信号与ROCK的调节联系起来，ROCK是一种丝氨酸/苏氨酸激酶，对单核细胞黏附和跨内皮细胞迁移具有强大的作用。本研究项目的总体目标是利用一个易于操作的细胞培养模型系统来确定CX3CL1驱动的单核细胞募集的关键调控机制，这将为开发体内牙周炎实验模型奠定基础。