Exploring the Mechanism of Immunological Responses in Liver Transplantation–From Rejection to Tolerance in DA-PVG Model
Date Issued
2009
Date
2009
Author(s)
Hsu, Teng-Kuei
Abstract
In this report, we have established a spontaneous tolerance model in which rats could develop spontaneous tolerance without any immunosuppressive treatments after orthotopic liver transplantion between DA (RT-1a) and PVG (RT-1c) rats. Functional proteomics analysis was introduced to investigate the differently expressed proteins involved in allograft liver transplantation. Among these different-expressed proteins, both haptoglobin and kininogen were reported to inhibit the proliferation of lymphocytes, suggesting a possible role of these two proteins in down-regulate cell-mediated graft rejection. Bioinformatics analysis of the statistically significant networks based on these differently expressed proteins indicated that the IL-6 signaling pathway might be involved in this model. IL-6 is a hepatoprotective cytokine that promotes liver regeneration, reduces liver injury and up-regulates the immune- suppressive proteins such as haptoglobin. Interestingly in this model, the highest expression of IL-6 occurred at the most severe stage of allograft rejection; thus we hypothesize that IL-6 might be the key contributor to spontaneous tolerance. Furthermore, it has been previously shown that IL-6 can also up-regulate the fucosylation regulatory genes, which supports our observation of an increase of fucosylation levels in serum protein; yet the related functions of fucosylation in this model remained unclear. These observations suggest that IL-6 plays a protective role in the spontaneous tolerance DA/PVG OLT model.
Subjects
orthotopic liver transplantion
immunosuppressive
allograft rejection
tolerance
proteomics
IL-6
kininogen
haptoglobin
File(s)![Thumbnail Image]()
Loading...
Name
ntu-98-R96b46018-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):39371b7c4033f24367a099471b9593a0