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Ann Hepatol. 2016 Sep-Oct;15(5):729-37. doi: 10.5604/16652681.1212524.

 Effects of combined genes of CTLA4Ig and IDO in post-liver transplantation immune tolerance of rats.

Author information

1
Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
2
Department of Hepatobiliary Surgery, Suining Central Hospital, Sichuan, P.R. China.

Abstract

 Background and rationale for the study. Previous studies showed that CTLA4Ig and indoleamine 2,3-dioxygenase (IDO) genes played regulatory role in organ transplantation but failed to reach satisfactory effects. In this study, we constructed an adenovirus- mediated gene expressing CTLA4Ig-IDO and established rat liver transplantation models. Recipients were randomly divided into four groups of 10 rats each. During the operation, CTLA4Ig, IDO, and CTLA4Ig-IDO genes, as well as a blank plasmid, were infused into different rat groups via portal vein to determine their effects on inducing immune tolerance. Survival rate of recipients, histological changes of graft liver, post-transplantation liver function, and cytokine levels were observed at day 14 after operation.

RESULTS:

Serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and total bilirubin level (TBIL) in the CTLA4Ig-IDO group were lower than those in the other three groups at 14 days post-transplantation (P < 0.05); mRNA and protein expressions of IL-2 and IFN-γ were higher in the control group, but lower in the CTLA4Ig-IDO group (P < 0.05). By contrast, expressions of IL-4, TGF-b, IL-10, and T lymphocyte apoptosis were higher in the CTLA4Ig-IDO group than those in the other three groups (P < 0.05). The CTLA4Ig-IDO group exhibited mild acute rejection and higher survival rate compared with the other groups (P < 0.05).

CONCLUSION:

Compared with using CTLA4Ig or IDO alone, combined transfection of CTLA4Ig-IDO was more effective in inducing immune tolerance after liver transplantation.

PMID:
27493112
DOI:
10.5604/16652681.1212524
[Indexed for MEDLINE]
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