FEASIBILITY STUDY--IDENTIFY AND CHARACTERIZE ENDOTHELIAL INFLAMMATION GENES

可行性研究——内皮炎症基因的识别和表征

• 批准号: 3728000
• 负责人: GEFFREY S KANSAS
• 金额: --
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3728000
• 关键词: SDS polyacrylamide gel electrophoresis; antisense nucleic acid; arthritis; autoimmune disorder; enzyme linked immunosorbent assay; gene expression; hybridomas; immunogenetics; immunoprecipitation; inflammation; molecular cloning; monoclonal antibody; northern blottings; nucleic acid hybridization; nucleic acid sequence; phenotype; polymerase chain reaction; protein structure function; tissue /cell culture; tumor necrosis factor alpha; vascular endothelium; western blottings

A central role for the vascular endothelium in inflammation has been appreciated for some time. However, the specific genetic programs responsible for induction and maintenance of an inflammatory state are only beginning to be identified and analyzed. An essential component of this analysis is the identification of genes which are expressed in endothelium activated by inflammatory stimuli, and which contribute to the leukocyte recruitment, morphological and biochemical changes in endothelium, and tissue damage characteristic of inflammation. This proposal details a broad approach to identifying such genes, and to identifying their possible role in inflammation. We will utilize a differential hybridization approach to identify genes which are expressed in endothelium activated by TNF-alpha, a prototypical inducer of inflammatory changes in endothelium, but which are not expressed in resting endothelium, and conversely, to identify genes whose expression is lost as a result of TNF-alpha treatment. Analysis of the function of these genes will be guided by their pattern of expression and homology to known genes and gene families. In addition, we will generate monoclonal antibodies which define activation-associated differences on the endothelial cell surface. This knowledge should provide the foundation for chemotherapeutic intervention in a broad range of inflammatory and autoimmune conditions, including rheumatoid arthritis, multiple sclerosis, atherosclerosis, and related disorders.

血管内皮在炎症中的核心作用