Abstract
Objective To explore the adeno-associated virus-mediated (AAV) programmed death ligand-1 (PD-L1) gene transfection effect in rats after liver transplantation interferon (INF)-γ,interleukin (IL)-17,IL-10 and transforming growth factor-β1 (TGF-β1).Methods All rats were divided into isogenic liver transplantation group (G1),allogeneic liver transplantation group (G2),allogeneic liver transplantation group infected by AAV2-RFP (Red fluorescent protein,RFP) (G3) and PD-L1-AAV2-RFP (G4).AAV mediated PD-L1 gene transfer was performed in LEW rat donor livers placed in BN recipients.Median surv ival time (MST) of grafts were investigated.The function of liver was measured with automatic biochemical analyser.The expressions of IL-10,IL-17,INF-γ and TGF-[β1 in liver were assessed by Enzyme linked immunosorbent assay (ELISA).Results Liver allograft survival was significantly prolonged by PD-L1-AAV2-RFP treatment [MST,29 (range:28-31) days] compared with either G2 or G3:18 (17-20) and 18 (17-19) days respectively (P＜0.05).In addition to G1 no expression of INF-γ,the remaining groups of transplanted liver INF-γ was similar to that of IL-17.G1 after 7 d IL-17 significantly increased,then decreased gradually to 28.9 ng/g,still higher than the first 3 d.G2 and G3 graft INF-γ,IL-17 has a strong start from the first 3 d expression gradually increased,both in 14 d reached the peak value 418.6,382.9 ng/g.Although G4 expression increased,its range and concentrations were significantly lower than G2 and G3.In addition G4 3 d,the difference was significant.Each group transplanted liver TGF-β1 and IL-10 expression characteristics similar,G1 significantly increased when postoperative 3 d to 170.2,106.2 ng/g,gradually decreased,but still higher than the G2 and G3.The G4 3 d its expression began to increase after the first peak 14 d which reached the value of 564.1,614.9 ng/g.Each group TGF-β1 and IL-10 concentrations were significantly higher rejection group except G4 3 d (P ＜ 0.05).Conclusion AAV-mediated gene transfer of PD-L1 into cold preserved liver allograft before transplantation results in long term survival of liver allograft.PD-L1 gene may take the effect in liver transplantation via suppression of INF-γ and IL-17 production as well as stimulation of IL-10 and TGF-β1 production. Key words: Programmed death ligand-1 ; Adeno-associated virus; Liver transplantation; Gene transfer; Inbred rat; Cytokines
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