REGULATION OF ICAM-1 IN ALVEOLAR EPITHELIAL CELLS

描述：（改编自申请人的摘要和具体目标。） 细胞间粘附分子-1（ICAM-1）是一种细胞表面粘附分子， 对淋巴细胞和单核细胞起重要作用的蛋白质 粘附和迁移，并参与关键的 活化T细胞的共刺激信号。 总目标 目的是阐明ICAM-1表达的调控 肺泡上皮细胞中。 为了实现这一目标， 将进行实验，检查大鼠细胞的原代培养物 作为II型上皮细胞分离，其在体外经历 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作用， 调控肺泡上皮细胞ICAM-1的表达。 具体目标 2将研究ICAM-1调节的分子生物学， 肺泡上皮细胞，关注蛋白质和mRNA的作用 周转以及mRNA转录的起始和延长。 在 此外，数据表明ICAM-1与细胞骨架蛋白相关。 元素，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 ICAM-1与细胞间相互作用的性质和调节 细胞骨架因此，本项目建议对以下方面的监管进行界定： 肺泡上皮细胞ICAM-1的表达，从启动 将基因转录成细胞中的大分子缔合物 面 这项工作可能会提供对监管的见解， 上皮细胞分化的肺泡空间，并可能提供 对一种分子表达的深入了解， 在定义肺泡腔的免疫环境中的作用。

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.