A human hepatic in vitro co-culture system for the analysis of DILI related signaling

The interaction between immune cells and hepatocytes during a sterile inflammation has come into focus in Drug-Induced Liver Injury (DILI) research during recent years. Therefore, this crosstalk was analysed in a novel indirect co-culture system with HepG2 and differentiated THP-1 cells using the antifungal drug ketoconazole as a known hepatotoxic model compound. The metabolism of ketoconazole, changes in the proteome, cytokine expression and secretion upon treatment in single- and co-culture were analysed. HepG2 metabolised ketoconazole to several metabolites which differed from those found in THP-1 cells both…