Innate immunity activation involved in unprotected porcine auto-transplant kidneys preserved by naked caspase-3 siRNA.
Innate immunity activation involved in unprotected porcine auto-transplant kidneys preserved by naked caspase-3 siRNA.
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裸 caspase-3 siRNA 保存的无保护猪自体移植肾中涉及的先天免疫激活
DOI：
10.1186/1479-5876-11-210
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发表时间：
2013-09-13
影响因子：
7.4
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Yang C;Li L;Xue Y;Zhao Z;Zhao T;Jia Y;Rong R;Xu M;Nicholson ML;Zhu T;Yang B
背景我们前期的研究发现，在低温保存过程中，经肾动脉灌注裸caspase-3小干扰RNA（siRNA）对自体移植猪肾有保护作用，但对炎症反应和细胞凋亡的增加无明显作用。所涉及的机制，特别是，是否siRNA或互补的系统反馈引发先天性免疫responses是值得进一步investigated.MethodsThe先天性免疫相关分子的蛋白质和mRNA的表达检测Western印迹和定量PCR在预先收集的组织从48 h自体移植肾。供体肾取自小型猪，用威斯康星州大学溶液（含或不含0.3 mg caspase-3 siRNA）冷保存24 h。结果Toll样受体（TLR）3、TLR 7及其主要接头TRIF和MyD 88在siRNA保存的自体移植肾中表达上调。NF-κB和c-Jun的mRNA水平增加，促炎细胞因子包括IL-1β、IL-6、TNF-α和干扰素（IFN）-α、β和γ的mRNA水平也增加。结论caspase-3 siRNA保存的自体移植肾中，先天免疫的激活和炎症反应的增强与TLR 3、TLR 7和PKR的增加有关，这可能是由于系统反馈的补充，尽管不能完全排除由短效caspase-3siRNA引发的持续作用。这些结果为指导未来siRNA设计和临床前研究提供了有价值的证据。
BackgroundThe naked caspase-3 small interfering RNA (siRNA) infused into the renal artery during cold preservation was effective, but did not protect auto-transplant porcine kidneys with increased inflammation and apoptosis in our previous study. The mechanisms involved, in particular, whether siRNA or complementary systemic feedback eliciting innate immune responses are worthy to be further investigated.MethodsThe protein and mRNA expression of innate immunity-related molecules were detected by western blotting and quantitative PCR in the tissues previously collected from 48 h auto-transplant kidneys. The donor kidneys were retrieved from mini pigs and cold preserved by University of Wisconsin solution with/without 0.3 mg caspase-3 siRNA for 24 h.ResultsThe protein level of Toll like receptor (TLR) 3, TLR7, and their main adapters, TRIF and MyD88, was up-regulated in the siRNA preserved auto-transplant kidneys. The mRNA level of NF-κB and c-Jun was increased, as well as pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α and interferon (IFN)-α, β and γ. In addition, the non-TLR RNA sensor PKR protein, but not RIG1, was also increased in the siRNA preserved auto-transplant kidneys.ConclusionsThe activation of innate immunity with amplified inflammatory responses in the caspase-3 siRNA preserved auto-transplant kidneys are associated with increased TLR3, TLR7 and PKR, which might be due to complementary systemic feedback, although persistent actions initiated by short-acting caspase-3 siRNA cannot be completely ruled out. These results provided valuable evidence to guide future siRNA design and pre-clinic studies.
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影响因子：
46.9
作者：
Judge, AD;Sood, V;MacLachlan, I
通讯作者：
MacLachlan, I
影响因子：
19.6
作者：
Chen, Jianlin;John, Reji;Richardson, James A.;Shelton, John M.;Zhou, Xin J.;Wang, Yanxia;Wu, Qing Qing;Hartono, John R.;Winterberg, Pamela D.;Lu, Christopher Y.
通讯作者：
Lu, Christopher Y.
裸Caspase 3小干扰RNA在猪肾冷保存中有效，但在自体移植中无效
影响因子：
2.2
作者：
Yang, Cheng;Jia, Yichen;Yang, Bin
通讯作者：
Yang, Bin
影响因子：
8.3
作者：
Leung PY;Stevens SL;Packard AE;Lessov NS;Yang T;Conrad VK;van den Dungen NN;Simon RP;Stenzel-Poore MP
通讯作者：
Stenzel-Poore MP
影响因子：
4
作者：
Kabilova, Tatyana O.;Meschaninova, Mariya I.;Chernolovskaya, Elena L.
通讯作者：
Chernolovskaya, Elena L.