Prolonged survival of islet allografts in mice treated with rosmarinic acid and anti-CD154 antibody.
- Author:
Da Yeon JUNG
1
;
Eun Young KIM
;
Sung Yeon JOO
;
Jae Berm PARK
;
Cheol MOON
;
Sa Hyun KIM
;
Eun Young SIM
;
Jae Won JOH
;
Choon Hyuck KWON
;
Ghee Young KWON
;
Sung Joo KIM
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: apoptosis; CD40 ligand; graft survival; immunosuppressive agents; islets of Langerhans transplantation; rosmarinic acid
- MeSH: Animals; Antibodies, Monoclonal/*pharmacology; Apoptosis/drug effects; CD40 Ligand/*immunology; Cinnamates/*pharmacology; Cytokines/biosynthesis; Depsides/*pharmacology; Diabetes Mellitus, Experimental; Flow Cytometry; Glucose/metabolism; Glucose Tolerance Test; Graft Survival/*drug effects; In Situ Nick-End Labeling; Injections, Intraperitoneal; Islets of Langerhans/drug effects/pathology; *Islets of Langerhans Transplantation; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Time Factors; Transplantation, Homologous
- From:Experimental & Molecular Medicine 2008;40(1):1-10
- CountryRepublic of Korea
- Language:English
- 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.
