A computational multi-scale model for the integration of paracrine stimuli activating NF-kB signalling in hepatocytes after lipopolysaccharide (LPS) treatment

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 comple…