Blockade of inducible costimulator pathway to prevent acute rejection in rat liver transplantation
Blockade of inducible costimulator pathway to prevent acute rejection in rat liver transplantation
复制标题
阻断诱导共刺激途径以防止大鼠肝移植中的急性排斥反应。
DOI：
10.1016/j.amjsurg.2008.09.014
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发表时间：
2009-08-01
影响因子：
3
通讯作者：
Gong, Jianping
中科院分区：
文献类型：
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作者：
Chen, Yong;Liu, Haizhong;Gong, Jianping
背景技术背景：方法：采用Lewis-to-Brown-Norway（BN）大鼠肝移植模型，观察小干扰RNA（siRNA）阻断诱导型共刺激分子（ICOS）对移植免疫的影响。CD 25/ICOS阳性细胞的数量，ICOS mRNA和蛋白水平，干扰素-γ和肿瘤坏死因子-α的水平测定。移植后第7天，CD 25/ICOS阳性细胞的频率减少，凋亡T细胞的频率增加。此外，我们发现，ICOS封锁可以抑制ICOS的mRNA和蛋白质的表达，降低干扰素-γ和肿瘤坏死因子-α的血浆水平，抑制细胞浸润到移植物中，并促进耐受性的干扰group.CONCLUSIONS：我们的数据表明，RNA干扰是一个有效的工具，下调ICOS的表达和保护alloggrafts从急性排斥反应。(c)2009 Elsevier Inc. All rights reserved.
BACKGROUND: The role of inducible costimulator (ICOS) in transplantation immunity remains unclear.METHODS: A Lewis-to-Brown-Norway (BN) rat liver transplant model was used to explore the effect of ICOS blockade by small interference RNA. Recipient survival rate, number of CD25/ICOS-positive cells, ICOS mRNA and protein levels, and interferon-gamma and tumor-necrosis factor-alpha levels were determined.RESULTS: Recipient survival was significantly prolonged in rats treated with RNA interference. On day 7 after transplantation, there was a diminished frequency of CD25/ICOS-positive cells and an increased frequency of apoptotic T cells. Furthermore, we found that ICOS blockade could inhibit mRNA and protein expression of ICOS, decrease plasma levels of interferon-gamma and tumor-necrosis factor-alpha, suppress cell infiltration into grafts, and promote tolerance in the interference group.CONCLUSIONS: Our data demonstrate that RNA interference is a potent tool to down-modulate ICOS expression and protect alloggrafts from acute rejection. (c) 2009 Elsevier Inc. All rights reserved.