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KMID : 0620920080400010001
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Experimental & Molecular Medicine
2008 Volume.40 No. 1 p.1 ~ p.10
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Prolonged survival of islet allografts in mice treated with rosmarinic acid and anti-CD154 antibody
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Jung Da-Yeon
Kwon Ghee-Young
Cho Jae-Won
Joo Sung-Yeon
Park Jae-Berm
Kwon Choon-Hyuck
Kim Sung-Joo
Kim Eun-Yonug
Moon Cheol
Kim Sa-Hyun
Sim Eun-Young
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Abstract
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Pancreatic islet transplantation can correct the abnormal glucose metabolism of Type 1 diabetes. Although immunosuppressants greatly reduce the acute rejection rate in transplant patients, the long-term side effects can be debilitating. Therefore, researchers are seeking to develop new immunosuppressive regimens that induce maximal levels of immunosuppression with minor side effects. Rosmarinic acid (Ros A) is a secondary metabolite of certain herbs and has multiple biological activities, including anti-inflammatory effects. Here, we have investigated whether treatment of mice with a combination of Ros A and anti-CD154 monoclonal antibody (MR1) improves islet allograft survival in a murine model. After transplantation, the mice were treated with either Ros A, MR1, or both (the "double" treatment). Allograft survival was prolonged in the double-treated animals compared to animals that received only Ros A or MR1. As is the case with the single-treated animals at 15 days after transplantation, the double-treated recipients did not display a significant decrease in the expression of cytokines or the population of activated T cells. Infiltrating CD3+ T cells were reduced in the MR1- or double therapy relative to control or RosA group. However, at the same time point, double-treated graft showed fewer apoptotic cells and increased expression of insulin and glucagons, compared to the single-treatment groups. Furthermore, long-term (＞ 150 days) allografts that were received with double therapy exhibited larger islet clusters and contained more insulin- and glucagon- positive cells, relative to the MR1-treated grafts. In conclusion, treatment with both Ros A and MR1 has a synergistic effect in murine islet allotransplantation.
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KEYWORD
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apoptosis, CD40 ligand, graft survival, immunosuppressive
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