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. ? ?
