Egr-1 and EtOH-induced hepatic leukocyte recruitment

Egr-1 和 EtOH 诱导的肝白细胞募集

• 批准号: 6994296
• 负责人: MICHELE T PRITCHARD
• 金额: $ 4.04万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 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 2006-07-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6994296
• 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（由申请人提供）：慢性乙醇暴露可导致肝损伤。我们的实验室已经证明，Egr-1对于早期乙醇性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，这两个因子在炎症期间对白细胞向肝脏募集都很重要。由于慢性乙醇增强lps刺激的Egr-1表达，我们假设Egr-1的增加调节ICAM-1、MCP-1和MIP-2的表达，并有助于早期乙醇诱导的肝损伤。该提案的具体目标将确定(1)Egr- 1是否调节ICAM-1、MCP-1和MIP-2的表达，以及(2)在慢性乙醇喂养后，这些基因在哪种细胞类型中表达。Egr-1作为炎症基因在缺血中介导组织损伤的主要调节因子。我们的研究结果将有助于我们了解Egr-1是否在乙醇性肝损伤中充当基因表达的“主开关”，因此可能成为乙醇性肝损伤治疗干预的新靶点。