Toll-like receptor 4 is a key mediator of murine steatotic liver warm ischemia/reperfusion injury.
Toll-like receptor 4 is a key mediator of murine steatotic liver warm ischemia/reperfusion injury.
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DOI：
10.1002/lt.21782
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发表时间：
2009-09
影响因子：
4.6
通讯作者：
Chavin, Kenneth D.
中科院分区：
文献类型：
--
作者：
Ellett, Justin D.;Evans, Zachary P.;Atkinson, Carl;Schmidt, Michael G.;Schnellmann, Rick G.;Chavin, Kenneth D.
脂肪变性供体由于原发性无功能发生率增加而经常被拒绝移植。这些移植物在移植过程中对缺血/再灌注（I/R）更敏感。再灌注前清除内毒素可改善I/R后肝脏功能。我们假设脂肪变性肝脏损伤的主要方式是Toll样受体4（TLR 4）信号传导。我们给4周龄的对照和TLR 4缺陷（TLR 4KO）小鼠喂食正常饮食（ND）或60%高脂饮食（HFD）4周以诱导脂肪变性。使小鼠经受全肝缺血（35分钟）和再灌注（1或24小时）。与对照HFD动物相比，TLR 4KO HFD动物在24小时时存活率改善并且肝脏病理学降低。浸润的研究显示，在对照HFD动物中，中性粒细胞和CD 4+细胞在24小时时增加，而TLR 4KO HFD动物与ND对照相似。在对照HFD动物中，白细胞介素6（IL-6）、IL-12和干扰素γ的信使RNA水平在1小时时升高，而TLR 4KO HFD动物与ND对照相似。与对照ND动物相比，对照HFD和TLR 4KO动物中再灌注1小时时的IL-10水平降低。总之，TLR 4 KO HFD动物中肝功能的这些改善暗示TLR 4是I/R后脂肪变性移植物衰竭的介导物。
Steatotic donors are routinely rejected for transplantation because of their increased rate of primary nonfunction. These grafts are more sensitive to ischemia/reperfusion (I/R) during transplantation. Removal of endotoxin before reperfusion improves liver performance post-I/R. We hypothesize that the main modality of injury in steatotic livers is toll-like receptor 4 (TLR4) signaling. We fed 4-week-old control and TLR4-deficient (TLR4KO) mice a normal diet (ND) or a 60% high-fat diet (HFD) for 4 weeks to induce steatosis. Mice were subjected to total hepatic ischemia (35 minutes) and reperfusion (1 or 24 hours). Survival improved and liver pathology decreased at 24 hours in TLR4KO HFD animals compared to control HFD animals. An investigation of infiltrates showed that neutrophils and CD4+ cells were increased at 24 hours in control HFD animals, whereas TLR4KO HFD animals were similar to ND controls. Messenger RNA levels of interleukin 6 (IL-6), IL-12, and interferon gamma were elevated at 1 hour in control HFD animals, whereas TLR4KO HFD animals were similar to ND controls. IL-10 levels at 1 hour of reperfusion in control HFD and TLR4KO animals were decreased versus control ND animals. In conclusion, these improvements in liver function in TLR4KO HFD animals implicate TLR4 as a mediator of steatotic graft failure after I/R.
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影响因子：
2.1
作者：
Fiorini, RN;Kirtz, J;Chavin, KD
通讯作者：
Chavin, KD
影响因子：
4.1
作者：
Emre, Yalin;Hurtaud, Corinne;Cassard-Doulcier, Anne-Marie
通讯作者：
Cassard-Doulcier, Anne-Marie
影响因子：
4.6
作者：
Shen, Xiu-Da;Ke, Bibo;Kupiec-Weglinski, Jerzy W.
通讯作者：
Kupiec-Weglinski, Jerzy W.
影响因子：
13.5
作者：
Shimizu, Y;Margenthaler, JA;Flye, MW
通讯作者：
Flye, MW
影响因子：
13.5
作者：
Selzner, M;Rüdiger, HA;Clavien, PA
通讯作者：
Clavien, PA