title: Gene silencing of 4-1BB by RNA interference inhibits acute rejection in rats with liver transplantation.
abstract: The 4-1BB signal pathway plays a key role in organ transplantation tolerance. In this study, we have investigated the effect of gene silencing of 4-1BB by RNA interference (RNAi) on the acute rejection in rats with liver transplantation. The recombination vector of lentivirus that contains shRNA targeting the 4-1BB gene (LV-sh4-1BB) was constructed. The liver transplantation was performed using the two-cuff technique. Brown-Norway (BN) recipient rats were infected by the recombinant LVs. The results showed that gene silencing of 4-1BB by RNAi downregulated the 4-1BB gene expression of the splenic lymphocytes in vitro, and the splenic lymphocytes isolated from the rats with liver transplantation. LV-sh4-1BB decreased the plasma levels of liver injury markers including AST, ALT, and BIL and also decreased the level of plasma IL-2 and IFN- γ in recipient rats with liver transplantation. Lentivirus-mediated delivery of shRNA targeting 4-1BB gene prolonged the survival time of recipient and alleviated the injury of liver morphology in recipient rats with liver transplantation. In conclusion, our results demonstrate that gene silencing of 4-1BB by RNA interference inhibits the acute rejection in rats with liver transplantation.
authors.affiliation: Department of General Surgery, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.forename: Shuqun
authors.initials: S
authors.lastname: Hu
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Song
authors.forename: Shengcai
authors.initials: S
authors.lastname: Yu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: Lei
authors.initials: L
authors.lastname: Qin
authors.forename: Haixin
authors.initials: H
authors.lastname: Qian
mesh_terms: D000818:Animals; D002460:Cell Line; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D016086:Lentivirus; D016031:Liver Transplantation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D051381:Rats; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic; D014184:Transplantation, Homologous; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9