Peptide Nucleic Acid Antisense Prolongs Skin Allograft Survival by Means of Blockade of CXCR3 Expression Directing T Cells into Graft

摘要: CXCR3, predominantly expressed on memory/activated T cells, is a receptor for both IFN-gamma-inducible protein 10/CXC chemokine ligand (CXCL)10 and monokine induced by IFN-gamma/CXCL9. It was reported that CXC chemokines 10/CXCL10 IFN-gamma/CXCL9 play critical role in the allograft rejection. We report CXCR3 dominant factor directing cells into mouse skin allograft, peptide nucleic acid (PNA) antisense significantly prolongs survival means of blockade expression allografts mice. found highly up-regulated spleen from BALB/c recipients day 7 receiving transplantation, whereas CCR5 moderately increased. designed PNA antisenses, i.v. treated mice received transplantations. The at dosage 10 mg/kg/day prolonged (17.1 +/- 2.4 days) compared with physiological saline treatment (7.5 0.7 days), (10 mg/kg/day) marginally (10.7 1.1 days). mechanism prolongation directly blocks which responsible to induce acute rejection, without interfering other functions cells. These results were obtained mRNA levels flow cytometry real-time quantitative RT-PCR technique, confirmed chemotaxis, Northern Western blot assays, histological evaluation grafts. present study indicates therapeutic potential prevent transplantation