Hepatocyte Transplantation-Induced Liver Inflammation Is Driven by Cytokines-Chemokines Associated With Neutrophils and Kupffer Cells

Background & Aims Hepatocyte transplantation-induced liver inflammation impairs cell engraftment. We defined whether proinflammatory cytokines and chemokines played roles in regulation of hepatocyte engraftment in the liver. Methods We performed studies over up to 3 weeks in rat hepatocyte transplantation systems. Expression of 84 cytokine-chemokine genes was studied by quantitative real-time polymerase chain reactions. Expression of selected up-regulated genes was verified by immunohistochemistry. Hepatic recruitment of neutrophils was demonstrated by myeloperoxidase activity assays, and Kupffer cell activation was established by carbon phagocytosis assays. The role of neutrophils and Kupffer cells in regulating expression of cytokine-chemokine genes as well as cell engraftment was determined by cell depletion studies. Results Within 6 hours after syngeneic cell transplantation, expression of 25 cytokine-chemokine genes increased by 2- to 123-fold, P Conclusions Cell transplantation-induced liver inflammation involves proinflammatory cytokine-chemokine systems capable of modulation by neutrophils and Kupffer cells. This offers new directions for optimizing cell therapy strategies.