Original pre-clinical sciencePPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class II–mismatched cardiac grafts
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Mice and reagents
Inbred male C57BL/6 (B6, H-2b) and B6.C-H-2bm12KhEg (BM12, H-2bm12) mice (6 to 8 weeks old, weight 20 to 25 g) were used in our study. The experimental protocol was approved by the Committee on the Use of Live Animals in Teaching and Research, University of Hong Kong.
Mouse heterotopic cardiac transplantation treatment protocols
Mouse cardiac transplantation was performed as previously described.13 Cardiac allografts from BM12 mice were transplanted heterotopically into C57BL/6 mice using standard microsurgical techniques for the transplantation of
Combined rosiglitazone and anti–IL-5 antibody treatment prolongs graft survival
In the MHC Class II–mismatched cardiac transplantation model for the syngeneic group (B6 to B6 as donor and recipient, respectively), 100% of the grafts survived >100 days. In the chronic rejection group (BM12 to B6) without treatment, the long-term survival rate was 35.7% (n = 14). The median survival time was 35 days with the earliest and latest times of rejection occurring at 20 and 48 days, respectively. With rosiglitazone treatment, the percentage of grafts surviving increased to 57.1% and
Discussion
In this report we have demonstrated that combined treatment with the PPAR-γ agonist rosiglitazone plus anti–IL-5 antibody prevents rejection of MHC Class II–histoincompatible cardiac grafts. We then analyzed the ability of these two compounds to modulate responses in the graft recipients that are associated with chronic rejection.
The ability of PPAR-γ agonists to reduce eosinophil recruitment into the airways has been observed in experimental models of ovalbumin-induced asthma.19, 20 In
Disclosure statement
The first two authors (Y.C. and D.-X.L.) contributed equally to this work. The project was supported by the General Research Fund (HKU 762108M) and the Seed Funding Programme for Basic Research, University of Hong Kong (200811159035).
The authors have no conflicts of interest to disclose.
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