Critical role of interferon regulatory factor-1 in murine liver transplant ischemia reperfusion injury.
Critical role of interferon regulatory factor-1 in murine liver transplant ischemia reperfusion injury.
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DOI：
10.1002/hep.23501
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发表时间：
2010-05
期刊：
影响因子：
13.5
通讯作者：
Geller, David A.
中科院分区：
文献类型：
--
作者：
Ueki, Shinya;Dhupar, Rajeev;Cardinal, Jon;Tsung, Allan;Yoshida, Junichi;Ozaki, Kikumi S.;Klune, John R.;Murase, Noriko;Geller, David A.
干扰素调节因子-1 （IRF-1）是免疫过程中调节基因表达的转录因子。我们假设IRF-1在肝移植（LTx）缺血/再灌注（I/R）损伤中起关键作用。野生型（WT） C57BL/6和IRF-1敲除（KO）小鼠在UW溶液中冷藏24小时后进行小鼠原位LTx。IRF-1在肝移植物中缺乏，而在受体中没有，导致肝细胞凋亡和肝损伤显著减少，并提高生存率。WT→WT LTx移植肝细胞中IRF-1 mRNA表达上调。移植物中IRF-1信号缺失导致肝细胞死亡配体和死亡受体mRNA水平显著降低，caspase-8活性降低，表明IRF-1介导了死亡配体诱导的肝细胞死亡。此外，WT移植物非实质细胞（NPC）中IRF-1 mRNA的上调幅度较小，但意义显著，且仅与NPC中IFN-γ mRNA的上调相关。IFN-γ mRNA在IRF-1 KO中显著降低。因此，移植肝细胞和NPC中的IRF-1在肝I/R损伤中具有不同的作用。然而，嵌合肝移植的LTx显示，缺乏肝细胞IRF-1的移植物比缺乏IRF-1的移植物在NPC中具有更好的保护作用。该研究确定了IRF-1在肝移植I/R损伤中的关键作用。
Interferon Regulatory Factor-1 (IRF-1) is a transcription factor that regulates gene expression during immunity. We hypothesize that IRF-1 plays a pivotal role in liver transplant (LTx) ischemia/reperfusion (I/R) injury. Mouse orthotopic LTx was conducted after 24 hours cold storage in UW solution in wild type (WT) C57BL/6 and IRF-1 knock out (KO) mice. IRF-1 deficiency in liver grafts, but not in recipients, resulted in significant reduction of hepatocyte apoptosis and liver injury, as well as improved survival. IRF-1 mRNA upregulation was typically seen in graft hepatocytes in WT→WT LTx. Deficiency of IRF-1 signaling in graft resulted in significantly reduced mRNA levels for death ligands and death receptors in hepatocytes, as well as decreased caspase-8 activities, indicating that IRF-1 mediates death ligand-induced hepatocyte death. Further, a smaller but significant IRF-1 mRNA upregulation was seen in WT graft non-parenchymal cells (NPC) and associated with IFN-γ mRNA upregulation exclusively in NPC. IFN-γ mRNA was significantly reduced in IRF-1 KO graft. Thus, IRF-1 in graft hepatocytes and NPC has distinct effects in hepatic I/R injury. However, LTx with chimeric liver grafts showed that grafts lacking hepatocellular IRF-1 had better protection compared to those lacking IRF-1 in NPC. The study identifies a critical role for IRF-1 in liver transplant I/R injury.
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影响因子：
32.4
作者：
Chaudhary, PM;Eby, M;Hood, L
通讯作者：
Hood, L
DOI：
10.1084/jem.20061097
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lappas CM;Day YJ;Marshall MA;Engelhard VH;Linden J
通讯作者：
Linden J
影响因子：
13.5
作者：
CYWES, R;GREIG, PD;STRASBERG, SM
通讯作者：
STRASBERG, SM
DOI：
10.1006/bbrc.1999.0276
发表时间：
1999-04-21
影响因子：
3.1
作者：
Kano, A;Haruyama, T;Watanabe, Y
通讯作者：
Watanabe, Y
影响因子：
6.2
作者：
FURUKAWA, H;TODO, S;STARZL, TE
通讯作者：
STARZL, TE