Figure 1.
Roles of NF-κB signaling in hepatocarcinogenesis. In the injury-promoted DEN hepatocarcinogenesis model, Kupffer cells are activated by IL-1α released from dying hepatocytes. Hepatocyte NF-κB (and p38α) inhibits this process by promoting hepatocyte survival. In low-grade, chronic, inflammation-promoted HCC models, hepatocytes with activated NF-κB produce cytokines and chemokines which activate Kupffer cells and recruit and activate other inflammatory cells and thereby maintain an inflammatory microenvironment. In both models, activated Kupffer cells produce cytokines and growth factors, such as IL-6, that are essential for the expansion of mutated hepatocytes and subsequent HCC development. Production of such cytokines by Kupffer cells is NF-κB dependent.