Knockdown of Interleukin-2 by shRNA-Mediated RNA Interference Prolongs Liver Allograft Survival

被引：15

作者：

Chen, Yong ^{[1
,2
]}

Yan, Tao ^{[1
,2
]}

Shi, Liu-jun ^{[3
]}

Liu, Zuojin ^{[1
,2
]}

Liang, Shao-yong ^{[1
,2
]}

Luan, Xiao-feng ^{[1
,2
]}

Long, Fei-wu ^{[1
,2
]}

Chen, Jie ^{[1
,2
]}

Peng, Yong ^{[1
,2
]}

Yan, Lue-nan ^{[3
]}

Gong, Jian-ping ^{[1
,2
]}

机构：

[1] Chongqing Med Univ, Affiliated Hosp 2, Chongqing Key Lab Hepatobliliary Surg, Chongqing 400010, Peoples R China

[2] Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobliliary Surg, Chongqing 400010, Peoples R China

[3] Sichuan Univ, W China Hosp, Liver Transplantat Ctr, Chengdu 610041, Peoples R China

来源：

JOURNAL OF SURGICAL RESEARCH | 2010年 / 159卷 / 01期

基金：

中国国家自然科学基金;

关键词：

interleukin-2; RNA interference; short hairpin RNA; liver transplantation; acute rejection; ANTISENSE OLIGONUCLEOTIDES; GENE-EXPRESSION; CYCLOSPORINE; SIRNAS; LYMPHOCYTES; RESPONSES; IMPACT;

D O I：

10.1016/j.jss.2008.09.019

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

Interleukin-2 (IL-2) plays a central role in T-cell activation, expansion, and homeostasis. The failure of IL-2 biosynthesis may play a critical role in tolerance induction. We tested the effect of IL-2 blockade by short hairpin RNA (shRNA) on regulating acute rejection in rat liver transplantation. To this end, we successfully designed and selected an effective interference plasmid, pIL-2B. The IL-2 mRNA expression level in the pIL-2B group was one-fifth of that in the no transfection group. Lewis to BN orthotopic liver transplant model was used to explore the effect of knockdown IL-2 by shRNA in vivo. Recipients treated with pIL-2-shRNA survived longer (median survival time of 16 d range 7-21 d) than those with empty vector (11; range 5-13) or saline (9; range 5-13) (P < 0.05), and was inferior to those with CsA (24; range 13-36, P < 0.05). The IL-2-shRNA attenuated acute rejection with decreased apoptosis of hepatocytes and reduced cytokine production of IL-2, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in the graft. Our results suggest that IL-2 targeting using RNA interference approach may be of potential interest in organ transplantation. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：582 / 587

页数：6

共 22 条

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