Prolonged survival of islet allografts in mice treated with rosmarinic acid and anti-CD154 antibody
Experimental & Molecular Medicine
;
: 1-10, 2008.
Article
in English
| WPRIM
| ID: wpr-219399
ABSTRACT
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Time Factors
/
Transplantation, Homologous
/
Cytokines
/
Islets of Langerhans Transplantation
/
Islets of Langerhans
/
Cinnamates
/
Apoptosis
/
In Situ Nick-End Labeling
/
CD40 Ligand
/
Diabetes Mellitus, Experimental
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2008
Type:
Article
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