Up-regulation of Galectin-9 in vivo results in immunosuppressive effects and prolongs survival of liver allograft in rats
Up-regulation of Galectin-9 in vivo results in immunosuppressive effects and prolongs survival of liver allograft in rats
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体内Galectin-9的上调导致免疫抑制作用并延长大鼠同种异体肝移植物的存活
DOI：
10.1016/j.imlet.2014.09.002
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发表时间：
2014-11-01
影响因子：
4.4
通讯作者：
Gong, Jian-Ping
中科院分区：
文献类型：
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作者：
Liu, Yi-Ming;Chen, Yong;Gong, Jian-Ping
背景和目的：急性排斥反应仍然是移植物功能障碍的主要原因，并会危及受者的移植后生存。目前的研究表明，半乳糖凝集素9（Gal-9）与促炎细胞因子的下调相关，因此具有负性免疫调节作用。但Gal-9在肝移植中的具体作用尚不清楚。方法：建立大鼠肝移植急性排斥反应模型（Lewis-BN，n=45），将受者随机分为三组：转染组（n=15）；空白质粒组（n=15）；和对照组（n = 15）。转染组冷缺血期经门静脉灌注Ad-galectin-9。空白质粒组灌流非目的载体，对照组灌流生理盐水。病理检查急性排斥反应；实时荧光定量PCR检测Gal-9、T-bet、ROR gamma t、GATA3、Foxp3 mRNA表达量； Western blotting和酶联免疫吸附法检测IFN-γ、IL-10和IL-17的表达。结果：转染组的病理变化较其他两组有所改善。转染组Gal-9 mRNA水平显着高于其他两组（*P < 0.05）；转染组中T-bet和ROR gamma t mRNA水平显着低于其他两组，而GATA3和Foxp3未显示出统计学显着性(*P < 0.05)。转染组的IFN-γ和IL-17水平显着低于其他两组（*蛋白和血清水平均P < 0.05）。结论：体内Gal-9的上调使免疫系统转向免疫抑制，并通过Th1/Th17的减少延长大鼠同种异体肝移植的存活。 (C) 2014 Elsevier B.V. 保留所有权利。
Background and objective: Acute rejection is still a major cause of graft dysfunction and would jeopardize recipients' post-transplantation survival. Current studies demonstrate that Galectin-9 (Gal-9) is associated with down-regulation of pro-inflammatory cytokines, thus, possesses a negative immune regulatory role. However, the specific role of Gal-9 in liver transplant remains unknown.Methods: To establish acute rejection models of rat liver transplantation (Lewis-BN, n = 45), recipients were randomly divided into following three groups: the transfected group (n = 15); the blank plasmid group (n = 15); and the control group (n = 15). The transfected group was perfused with Ad-galectin-9 through the portal vein during the cold ischemia period. The blank plasmid group was perfused with non-target vector, and the control group was perfused with saline. The acute rejection was assayed by pathological examination; Gal-9, T-bet, ROR gamma t, GATA3 and Foxp3 mRNA expression was detected by real-time PCR; Western blots and enzyme-linked immunosorbent assays were performed to measure IFN-gamma, IL-10 and IL-17 expression.Results: The pathological change of the transfected group was ameliorated than that of the other two groups. The Gal-9 mRNA level in the transfected group was much higher than that in the other two groups (*P < 0.05); T-bet and ROR gamma t mRNA levels were significantly lower in the transfected group than in the other two groups while GATA3 and Foxp3 were not shown statistics significances (*P < 0.05). The IFN-gamma and IL-17 levels in the transfected group were significantly lower than in the other two groups (*P < 0.05 for both protein and serum levels).Conclusion: Up-regulation of Gal-9 in vivo turns immune system toward immnuosuppression and prolongs rats liver allograft survival by the diminishment of Th1/Th17. (C) 2014 Elsevier B.V. All rights reserved.