p20, Molecular Shortstop for Inflammatory Lung Diseases

p20，炎症性肺病的分子游击剂

• 批准号: 6485715
• 负责人: KENNETH L BRIGHAM
• 金额: $ 27.49万
• 依托单位: GENERX+, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-20 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6485715
• 关键词: adult respiratory distress syndrome; antiinflammatory agents; cystic fibrosis; drug design /synthesis /production; gene delivery system; gene therapy; inflammation; interleukin 6; interleukin 8; liposomes; lung disorder; recombinant proteins; respiratory epithelium; transcription factor; transfection; transfection /expression vector

DESCRIPTION (Applicant's abstract): The transcription factor CAAT enhancer binding protein beta (C/EBPbeta) is a key factor orchestrating the inflammatory response. Specifically, expression of the genes encoding the pro-inflammatory cytokines IL-6 and on IL-8 are regulated by C/EBPbeta. C/EBPbeta can be either an activator or an inhibitor of inflammation depending on the dominant isoforms produced. Our data indicate that airway epithelial cells in culture terminate production of IL-6 and IL-8 increasing production of inhibitory C/EBPbeta isoform (p20) and that cells that have an exaggerated inflammatory response produce decreased amounts of this isoform. In addition, when animals are given endotoxin there is a decrease in lung production of the inhibitory C/EBPbeta isoform and an increase in production of the activator isoform. Since IL-6 production correlates with severity of sepsis in humans and interventions that decrease IL-6 improve outcome in that setting, we believe that increasing the inhibitory C/EBPbeta isoform in the lungs could be therapeutic for the pulmonary complications of sepsis.

描述（申请人的摘要）：转录因子CAAT增强器 结合蛋白β（C/EBPBETA）是策划炎症的关键因素 回复。具体而言，编码促炎的基因的表达 细胞因子IL-6和IL-8受C/EBPBETA调节。 C/ebpbeta可以是 根据主要同工型的激活剂或炎症抑制剂 生产。我们的数据表明培养物中的气道上皮细胞终止 IL-6和IL-8的产生增加了抑制性C/EBPBETA的产生 同工型（P20）和具有夸张炎症反应的细胞 产生减少的同工型。另外，当动物被给予 内毒素抑制性C/EBPBETA的肺产生降低 同工型和激活剂同工型的产生增加。自IL-6以来 生产与人类败血症的严重程度和干预措施相关 减少IL-6在这种情况下改善结果，我们认为增加 肺中的抑制性C/EBPBETA同工型可以治疗 败血症的肺并发症。