Prolonged survival of islet allografts in mice treated with rosmarinic acid and anti-CD154 antibody

• Published in: Experimental & molecular medicine Vol. 40; no. 1; pp. 1 - 10
• Main Authors: Jung, Da-Yeon, Kim, Eun-Young, Joo, Sung-Yeon, Park, Jae Berm, Moon, Cheol, Kim, Sa Hyun, Sim, Eun-Young, Joh, Jae-Won, Kwon, Choon Hyuck, Kwon, Ghee-Young, Kim, Sung-Joo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.02.2008; Springer Nature B.V; Korean Society of Medical Biochemistry and Molecular Biology
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; 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; Islets of Langerhans - pathology; Islets of Langerhans Transplantation; Male; Medical Biochemistry; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Medicine; Original; Rosmarinic Acid; Stem Cells; Time Factors; Transplantation, Homologous; immunosuppressive agents; graft survival; apoptosis; rosmarinic acid; islets of Langerhans transplantation; CD40 ligand
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2008.40.1.1

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.