Background: Bacterial lipopolysaccharide (LPS) efficiently stimulates the secretion of tumor necrosis factor (TNF)-α from non-parenchymal Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs). Paracrine-acting TNFα subsequently activates the canonical NF-kB pathway in hepatocytes, which is a central regulator of acute phase protein expression and the inflammatory response. However, the impact of individual liver cell types on this pro-inflammatory response has not been sufficiently analysed i.a. due to technical limitations. To establish a holistic view on this complex multi-scale process in a quantitative and time-resolved manner, systems biology serves as a valuable tool.

The cytokine tumor necrosis factor (TNF)-α is a key factor in the priming phase of liver regeneration since it activates the NF-κB signalling pathway, which primes hepatocyte for proliferation. In order to understand how TNFα-dependend NF-κB activation contributes to a cellular response in parenchymal liver cells, we aimed to generate a hepatocyte-specific mathematical model based on quantitative and time-resolved data of NF-κB pathway constituents after TNFα administration.