Project 1

The liver is the largest solid organ in the body with dual inputs for its blood supply. It receives 80% of its blood supply from the gut through the portal vein, which is rich in bacterial products, environment toxins, and food antigens. The remaining 20% is from vascularization by the hepatic artery. 70% of the cell number or 80% of the liver volume is composed of hepatocytes that fulfill the metabolic and detoxifying needs of the body. The remaining cells are made up of nonparenchymal cells, including endothelial cells, stellate cells, Kupffer cells, and lymphocytes. The liver successfully combines the role of a biochemical laboratory with the role of a major organ of innate immunity. In a physiologically relevant state, it eliminates antigens derived from the gastrointestinal tract, aging and transformed cells and reveals tolerance to their continuous presence. The liver responses by organ regeneration to partial hepatectomy and by acute phase response to any kind of body injury not affecting the liver.

Our recent studies revealed the transient upregulation of interferon a (IFNa) expression during the early hours after partial hepatectomy. To unravel the potential role of IFNa in liver restoration we addressed the gene expression in primary hepatocytes isolated from control liver and cultivated with quasiphysiological dose of IFNa. ISGylation-related genes responsible for post-translational protein modification were the earliest up-regulated genes. Their expression and regulation after partial hepatectomy and laparotomy are in the centre of our attention. The unexpected results raised the question on the role of these genes in acute phase response and the mechanism of their IFNa independent regulation. The analysis of corresponding genes promoters with consequent chromatin immunoprecipitation is going on. The function of IFNa after partial hepatectomy is still an exciting challenge.