Role of the innate immune system in animal models of living donor liver transplantation

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In living donor liver transplantation (LDLT), the innate immune system plays an important role in regulating the regeneration of the remnant liver and the transplant as well as damaging inflammatory processes (e.g., ischemia/reperfusion injury, rejection, infections) in the transplant, respectively. Since it has been suggested that the Toll-Like-Receptor (TLR)- system may be crucial for these events, we would like to investigate its role in LDLT, TLR 1-9 agonists will be tested for their ability to induce or suppress pro- or anti-regenerative cytokines and signaling molecules in isolated parenchyma! and non-parenchyma! liver cells. In a rat model of LDLT, donor and recipient are pretreated with TLR agonists before liver resection or transplantation, respectively, and clinical outcome, histological, biochemical and molecular changes are assessed postoperatively. To investigate if Kupffer cells are involved in any TLR-mediated effects these experiments are performed with or without GdClpretreatment. Finally, IRF-3 and MyD88 knockout mice will be used to further investigate the role of the TLR-mediated signaling pathways after partial liver resection. Ultimately, these experiments are aimed improving the clinical outcome of LDLT by targeted modulation of the TLR-system.