Abstract:Objective:To identify the effect of peptide nucleic acid of CC chemokine receptor 5 on acute rejection of islet allograft.
Methods :Mice islet transplant models were used to test the effect of PNA CCR5 by targeting CCR5 in acute allograft rejection. In vitro T cell proliferative responses were assessed by mixed lymphocyte response(MLR). RT-PCR and Western blot were used to detect the expression of mRNA and protein.
Results:PNA CCR5-treated recipients demonstrated statistically significant prolongation［(12.00±1.75)d］ in functional allograft survival when compared with saline［(6.50±0.58)d］ or PNA mismatch-treated recipients［(6.50±0.50) d］. The CCR5 mRNA expression level of PNA CCR5, control, and PNA mismatch treatment recipients at day 7 posttransplant was 0.56±0.05, 1.68±0.07 and 1.80±0.14, respectively. The data showed that CCR5 protein was significantly down-regulated in PNA CCR5 treatment allografts compared with saline and PNA mismatch treatment allografts(P＜0.01, P＜0.01). Lymphocytes from PNA CCR5 treatment mice also exhibited a reduced degree of proliferation.
Conclusions:The present study indicates that PNA CCR5 can prolong the survival time of islet allograft, and has a potential therapeutic effect on inhibiting acute allograft rejection.