REGULATION OF MOTILITY AND TRANSCRIPTION IN INFLAMMATION

炎症中运动和转录的调节

• 批准号: 6300943
• 负责人: Kenneth A Jacobson
• 金额: $ 11.68万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6300943
• 关键词: actins; atomic force microscopy; biomechanics; calcium flux; calcium indicator; cell adhesion molecules; cell migration; cell motility; chemokine; chemotaxis; confocal scanning microscopy; gel mobility shift assay; genetic transcription; guanine nucleotide binding protein; human tissue; immunoconjugates; inflammation; interference microscopy; photoactivation; tissue /cell culture; vascular endothelium permeability; video microscopy

Cell movement is an essential component of the inflammatory response. After arrest of circulating leukocytes on the endothelial layer, leukocytes move to the site of extravasation, undergo diapedesis, and finally migrate to sites of infection. In these processes, various types of leukocytes will be recruited and guided by chemotactic gradients mediated by a class of cytokines, the soluble chemokines, or by other molecules bound to the endothelial cell surface. Our overall objective is to investigate how the regulation of cell motility is coordinated with transcription during inflammation. The general hypothesis of this proposal is that the movement of cells participating in the inflammatory response is coupled to the transcription of certain genes that code for various cytokines. This is thought to occur via factors, including intracellular calcium and the Rho family of small GTP-binding proteins, regulating the organization, dynamics and biomechanical properties of cells and, in turn, their motile behavior. A related aspect of this work will address how cell locomotion is linked to gene expression via transcriptional regulation. We will then study the regulation of motile events in the process of leukocyte extravasation through the endothelium. A novel aspect of this proposal is that most of these studies will be conducted on individual cells using imaging and new photomanipulative techniques.

细胞运动是炎症反应的重要组成部分。在内皮层上捕捉循环白细胞后，白细胞移至渗出的部位，进行尿和最终迁移到感染部位。在这些过程中，将由一类细胞因子，可溶性趋化因子或与内皮细胞表面结合的其他分子介导的趋化梯度募集和指导各种类型的白细胞。我们的总体目的是研究细胞运动的调节如何与炎症过程中的转录协调。该提议的一般假设是，参与炎症反应的细胞运动与某些为各种细胞因子编码的基因的转录耦合。人们认为这是通过因素发生的，包括细胞内钙和小型GTP结合蛋白的Rho家族，调节细胞的组织，动力学和生物力学特性以及其动向行为。这项工作的一个相关方面将解决细胞运动如何通过转录调节与基因表达联系起来。然后，我们将研究通过内皮的白细胞渗出过程中运动事件的调节。该提案的一个新方面是，这些研究中的大多数将使用成像和新的照相技术对单个细胞进行。