Tumor Necrosis Factor-伪-Induced Protein 8-Like 2 Gene Overexpression Prolongs the Survival of Rat Allogeneic Heart Allografts

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• 作者：Z. Youbin ; Y. Yunsheng ; ^{yys700826@sina.com" class="auth_mail" title="E-mail the corresponding author} ; S. Zhenya ; Z. Xiaoming ; T. Xiaomei
• 刊名：Transplantation Proceedings
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：47
• 期：8
• 页码：2517-2522
• 全文大小：1086 K

文摘

The objective of the study was to examine whether overexpression of the tumor necrosis factor-伪–induced protein 8–like 2 (TNFAIP8L2; TP8L2) gene might prolong the survival of a rat heart allograft and to explore the possibility of gene-induced immune tolerance and its specific mechanisms of action in rats.

Methods

A gene vector (AdC68) was constructed of a rat's TP8L2 gene to overexpress the TP8L2 gene in the models. The Wistar-to-Dawley rat allogeneic heart allograft models were created and randomly separated into 5 groups: control, no treatment after surgery; Fk506, treated with immune inhibitor FK506 0.5 mg/kg/d after surgery; TP8L2, treated with 0.25 × 10⁹ Pfu recombinant TP8L2 adenovirus after surgery; FK506+TP8L2, treated with FK506 0.25 mg/kg/d and 0.25 × 10⁹ Pfu recombinant TP8L2 adenovirus after surgery; and no-TP8L2, treated with 0.25 × 10⁹ Pfu recombinant adenovirus without TP8L2 gene overexpression after surgery. We also examined whether the overexpressed TP8L2 gene can prolong the donor heart's mean survival time and detect the changes of various related indicators.

Results

The survival time of the donor heart in the TP8L2 and FK506+TP8L2 groups was significantly longer than that in the remaining groups; the difference was statistically significant (P < .05). The percentage of CD4⁺CD25⁺ regulatory T cells in the TP8L2 and FK506+TP8L2 groups was significantly higher than that in the remaining groups; the difference was statistically significant (P < .05). The expression of interleukin (IL)-2, tumor necrosis factor-伪, and interferon-纬 in the FK506+TP8L2 group was significantly lower and the expression of IL-4 and IL-10 was significantly higher than those in other groups; the differences in cytokine levels were significant (P < .05).

Conclusions

TP8L2 plays an important role in the induction of immune tolerance in heart allografts.