REGULATION OF ICAM-1 IN ALVEOLAR EPITHELIAL CELLS

描述：(根据申请者的抽象和具体目标改编。) 细胞间黏附分子-1(ICAM-1)是一种细胞表面黏附 对淋巴细胞和单核细胞起重要作用的蛋白质 坚持和迁移，并参与关键基因的转导 T细胞激活的共刺激信号。总目标 其应用的目的是阐明ICAM-1的表达调控 在体外培养的肺泡上皮细胞中。为了实现这一目标， 将进行实验，检测大鼠细胞的原代培养 分离的作为II型上皮细胞的体外试验 向I型细胞表型分化。具体目标我会 描述可能涉及的一组选定信号的角色 肺泡上皮细胞ICAM-1表达的调控。特定目标 2将研究ICAM-1调控的分子生物学 肺泡上皮细胞蛋白和信使核糖核酸的作用 MRNA转录的启动和延伸。在……里面 此外，数据表明ICAM-1与细胞骨架有关 元素，而ICAM-1的功能活性可能取决于 与细胞骨架的相互作用。具体目标3将决定 细胞间黏附分子-1与血管内皮生长因子相互作用的性质和调控 细胞骨架。因此，本项目建议定义以下规则 肺泡上皮细胞间黏附分子-1的表达 基因转录到细胞中的大分子缔合 浮出水面。这项工作可能会为监管提供洞察力 上皮细胞在肺泡腔中的分化并可能提供 对分子表达的洞察可能起到关键作用 在确定肺泡腔免疫环境中的作用。

DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.) Intercellular adhesion molecule-1 (ICAM-1) is a cell surface adhesion protein that plays an important role for lymphocyte and monocyte adherence and migration and is involved in the transduction of critical co-stimulatory signals for the activation of T cells. The overall goal of the application is to elucidate the regulation of ICAM-1 expression in alveolar epithelial cells in vitro. To accomplish this objective, experiments will be performed examining primary cultures of rat cells isolated as type II epithelial cells which undergo in vitro differentiation towards the type I cell phenotype. Specific Aim I will delineate the roles of a selected set of signals that may be involved in the control of alveolar epithelial cell ICAM-1 expression. Specific Aim 2 will investigate the molecular biology of ICAM-1 regulation in alveolar epithelial cells, focusing of the roles of protein and mRNA turnover, and initiation and elongation of mRNA transcription. In addition, data suggest that ICAM-1 is associated with cytoskeletal elements, and the functional activity of ICAM-1 may depend on the interaction with the cytoskeleton. Specific Aim 3 will determine the nature and regulation of this interaction between ICAM-1 and the cytoskeleton. Thus this project proposes to define the regulation of alveolar epithelial ICAM-1 expression from the initiation of transcription of the gene to the macromolecular associations at the cell surface. The work may provide insights into the regulation of epithelial cell differentiation in the alveolar space and may provide insights into the expression of a molecule which may play a critical role in defining the immunologic milieu of the alveolar space.