Our hepatic co-cultures using kupffer cells are powerful new in vitro tools for modeling the liver. Hepatocyte monocultures have served as the standard in vitro model for ADME/Tox-related research, including metabolism and drug-drug interactions. However, a growing body of evidence demonstrates (1-7) that monocultures of hepatocytes alone are not always predictive of certain physiological conditions.
Growing evidence (1-7) shows that under both normal and pathological conditions, many hepatocyte functions are regulated by substances released from neighboring non-parenchymal cells (NPC). These cells, particularly Kupffer cells, play an important role in the modulation of xenobiotic metabolism in the liver. Studies indicate that co-culture of hepatocytes with kupffer cells would better represent both normal liver physiology as well as disease states.
Figure 1: Model normal and inflamed liver states. These models enable researchers to study the interactions between hepatocytes and Kupffer cells during liver inflammation.
Figure 2: IL6 production in Kupffer cells after LPS and IL2 stimulation for 24, 48 and 72 hrs. As expected, following activation with LPS treatment, IL6 production is significantly up-regulated at 24 hrs and then progressively decreases, suggesting desensitization of Kupffer cells to chronic stimulation with LPS.
Figure 3: IL6 production in Kupffer cells and hepatocyte co-cultures after LPS and IL2 stimulation for 24, 48 and 72 hrs. Note that IL6 is significantly up-regulated in co-cultures at all time points of 24, 48 and 72 hrs. This suggests cellular self assembly between Kupffer cells and hepatocytes that synergistically allows those cells to function together during resolution of inflammation.
Figure 4: Modulation of CYP3A23 and CYP1A2 enzyme activities in co-cultures after LPS and IL2 stimulation for 72 hrs. Note near 80% decrease of CYP3A23 and CYP1A2 after IL2 treatment.
For Research Use Only. Not for use in diagnostic procedures.