Yi-Ming Liu1, Yong Chen2, Jin-Zheng Li3, Jian-Ping Gong4. 1. Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, 76# Linjiang Road, Chongqing 400010, China. Electronic address: ncisgibbs@163.com. 2. Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, 76# Linjiang Road, Chongqing 400010, China. Electronic address: doctorcy007@163.com. 3. Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, 76# Linjiang Road, Chongqing 400010, China. Electronic address: vitamin198305@163.com. 4. Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, 76# Linjiang Road, Chongqing 400010, China. Electronic address: gongjianping11@126.com.
Abstract
BACKGROUND AND OBJECTIVE: Acute rejection is still a major cause of graft dysfunction and would jeopardize recipients' post-transplantation survival. Current studies demonstrate that Galectin-9 (Gal-9) is associated with down-regulation of pro-inflammatory cytokines, thus, possesses a negative immune regulatory role. However, the specific role of Gal-9 in liver transplant remains unknown. METHODS: To establish acute rejection models of rat liver transplantation (Lewis-BN, n = 45), recipients were randomly divided into following three groups: the transfected group (n = 15); the blank plasmid group (n = 15); and the control group (n = 15). The transfected group was perfused with Ad-galectin-9 through the portal vein during the cold ischemia period. The blank plasmid group was perfused with non-target vector, and the control group was perfused with saline. The acute rejection was assayed by pathological examination; Gal-9, T-bet, RORγt, GATA3 and Foxp3 mRNA expression was detected by real-time PCR; Western blots and enzyme-linked immunosorbent assays were performed to measure IFN-γ, IL-10 and IL-17 expression. RESULTS: The pathological change of the transfected group was ameliorated than that of the other two groups. The Gal-9 mRNA level in the transfected group was much higher than that in the other two groups (*P < 0.05); T-bet and RORγt mRNA levels were significantly lower in the transfected group than in the other two groups while GATA3 and Foxp3 were not shown statistics significances (*P < 0.05). The IFN-γ and IL-17 levels in the transfected group were significantly lower than in the other two groups (*P < 0.05 for both protein and serum levels). CONCLUSION: Up-regulation of Gal-9 in vivo turns immune system toward immnuosuppression and prolongs rats liver allograft survival by the diminishment of Th1/Th17.
BACKGROUND AND OBJECTIVE: Acute rejection is still a major cause of graft dysfunction and would jeopardize recipients' post-transplantation survival. Current studies demonstrate that Galectin-9 (Gal-9) is associated with down-regulation of pro-inflammatory cytokines, thus, possesses a negative immune regulatory role. However, the specific role of Gal-9 in liver transplant remains unknown. METHODS: To establish acute rejection models of rat liver transplantation (Lewis-BN, n = 45), recipients were randomly divided into following three groups: the transfected group (n = 15); the blank plasmid group (n = 15); and the control group (n = 15). The transfected group was perfused with Ad-galectin-9 through the portal vein during the cold ischemia period. The blank plasmid group was perfused with non-target vector, and the control group was perfused with saline. The acute rejection was assayed by pathological examination; Gal-9, T-bet, RORγt, GATA3 and Foxp3 mRNA expression was detected by real-time PCR; Western blots and enzyme-linked immunosorbent assays were performed to measure IFN-γ, IL-10 and IL-17 expression. RESULTS: The pathological change of the transfected group was ameliorated than that of the other two groups. The Gal-9 mRNA level in the transfected group was much higher than that in the other two groups (*P < 0.05); T-bet and RORγt mRNA levels were significantly lower in the transfected group than in the other two groups while GATA3 and Foxp3 were not shown statistics significances (*P < 0.05). The IFN-γ and IL-17 levels in the transfected group were significantly lower than in the other two groups (*P < 0.05 for both protein and serum levels). CONCLUSION: Up-regulation of Gal-9 in vivo turns immune system toward immnuosuppression and prolongs rats liver allograft survival by the diminishment of Th1/Th17.