Egr-1 and EtOH-induced hepatic leukocyte recruitment

Egr-1 和 EtOH 诱导的肝白细胞募集

• 批准号: 7134300
• 负责人: MICHELE T PRITCHARD
• 金额: $ 5.04万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-26 至 2007-09-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7134300
• 关键词: Kupffer' s cell; cell adhesion molecules; cell type; cellular pathology; ethanol; gene expression; genetic regulation; genetically modified animals; immunocytochemistry; inflammation; laboratory mouse; leukocyte activation /transformation; lipopolysaccharides; liver disorder; macrophage inflammatory proteins; molecular pathology; monocyte chemoattractant protein 1; postdoctoral investigator; protein localization; regulatory gene; transcription factor

DESCRIPTION (provided by applicant): Chronic ethanol exposure can lead to hepatic injury. Our lab has demonstrated that Egr-1 is essential for the development of early, ethanol-induced liver injury. Egr-1 either directly or indirectly regulates the adhesion molecule ICAM-1 and the chemokines MCP-1 and MIP-2, each of which is important for leukocyte recruitment to the liver during inflammation. Because chronic ethanol enhances LPS-stimulated Egr-1 expression, we hypothesize that increased Egr-1 regulates ICAM-1, MCP-1 and MIP-2 expression and contributes to early ethanol-induced liver injury. The Specific Aims of this proposal will determine (1) if Egr- 1 regulates ICAM-1, MCP-1 and MIP-2 expression and (2) in which cell types these genes are expressed after chronic ethanol feeding. Egr-1 functions as a master regulator of inflammatory genes mediating tissue damage in ischemia. Results of our studies will contribute to our understanding of whether Egr-1 acts as a 'master switch' for gene expression in ethanol-induced liver injury and therefore may be a novel target for therapeutic intervention in ethanol-induced liver injury.

描述（由申请方提供）：长期乙醇暴露可导致肝损伤。我们的实验室已经证明Egr-1对于早期乙醇诱导的肝损伤的发展至关重要。Egr-1直接或间接调节粘附分子ICAM-1和趋化因子MCP-1和MIP-2，它们中的每一种对于炎症期间白细胞向肝脏的募集都是重要的。由于慢性乙醇可增强LPS刺激的Egr-1表达，我们推测Egr-1的增加可调节ICAM-1、MCP-1和MIP-2的表达，并有助于早期乙醇诱导的肝损伤。本提案的具体目的将确定（1）Egr- 1是否调节ICAM-1、MCP-1和MIP-2表达，以及（2）慢性乙醇喂养后这些基因在哪些细胞类型中表达。Egr-1作为炎症基因的主要调节因子介导缺血性组织损伤。我们的研究结果将有助于我们了解Egr-1是否作为乙醇诱导的肝损伤中基因表达的“主开关”，因此可能是乙醇诱导的肝损伤治疗干预的新靶点。