A Role for MK2 in Enhancing Neutrophil-Derived ROS Production and Aggravating Liver Ischemia/Reperfusion Injury.
A Role for MK2 in Enhancing Neutrophil-Derived ROS Production and Aggravating Liver Ischemia/Reperfusion Injury.
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DOI：
10.3389/fimmu.2018.02610
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发表时间：
2018
影响因子：
7.3
通讯作者：
Qian F
中科院分区：
文献类型：
--
作者：
Sun L;Wu Q;Nie Y;Cheng N;Wang R;Wang G;Zhang D;He H;Ye RD;Qian F
炎症反应和活性氧的增加是肝缺血再灌注损伤的重要原因，但其调控机制尚未完全阐明。在这里，我们报告了MAPK活化蛋白激酶2（MK2）的遗传缺陷可以保护MK2−/−小鼠免受肝脏I/R损伤并减少肝脏中性粒细胞积聚。中性粒细胞耗竭减轻野生型小鼠肝脏I/R损伤。在对C5 a刺激的反应中，MK2−/−中性粒细胞产生较少的超氧化物，其中NADPH氧化酶活化和p47 phox磷酸化均降低。此外，p47 phox的Ser 329被鉴定为增强超氧化物的产生。丝氨酸329磷酸化在MK2−/−中性粒细胞中减少。为了确定MK2是否通过激活中性粒细胞来调节肝脏I/R损伤，我们产生了骨髓特异性MK2缺失小鼠（MK2 Lyz 2 −KO），并且MK2 Lyz 2 −KO小鼠的肝脏I/R损伤减少。我们的研究结果表明，MK2增强肝I/R损伤，并诱导ROS的产生，增加p47 phox磷酸化和MK2是一个潜在的药物靶点，用于治疗肝I/R损伤。
Increased inflammatory responses and enhanced reactive oxygen species contribute to hepatic ischemia/reperfusion (I/R) injury, however the modulatory mechanisms haven't been completely unveiled. Here, we report that genetic deficiency of MAPK-activated protein kinase 2 (MK2) protected against hepatic I/R injury and decreased hepatic neutrophil accumulation in MK2−/− mice. Depletion of neutrophil attenuated hepatic I/R injury in wide type mice. In response to C5a stimulation, MK2−/− neutrophils generated less superoxide in which both NADPH oxidase activation and p47phox phosphorylation were decreased. Furthermore, Ser329 of p47phox was identified for enhancement of superoxide production. The Ser329 phosphorylation was reduced in MK2−/− neutrophils. To determine whether MK2 modulates hepatic I/R injury via activating neutrophils, we generated myeloid-specific MK2 deletion mice (MK2Lyz2−KO) and liver I/R injury was reduced in MK2Lyz2−KO mice. Our results indicate that MK2 augments hepatic I/R injury and induces ROS production with increased p47phox phosphorylation and MK2 is a potential drug target for treating hepatic I/R injury.
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影响因子：
3.9
作者：
Samulin Erdem J;Skaug V;Haugen A;Zienolddiny S
通讯作者：
Zienolddiny S
影响因子：
4.4
作者：
Honda, Masaki;Takeichi, Takayuki;Inomata, Yukihiro
通讯作者：
Inomata, Yukihiro
DOI：
10.1186/1476-9255-7-27
发表时间：
2010-05-28
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Lutz J;Thürmel K;Heemann U
通讯作者：
Heemann U
影响因子：
5.8
作者：
Makni-Maalej, Karama;Chiandotto, Melanie;El-Benna, Jamel
通讯作者：
El-Benna, Jamel
损伤相关分子模式激活的中性粒细胞胞外陷阱加剧了无菌性炎症性肝损伤。
DOI：
10.1002/hep.27841
发表时间：
2015-08
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Huang H;Tohme S;Al-Khafaji AB;Tai S;Loughran P;Chen L;Wang S;Kim J;Billiar T;Wang Y;Tsung A
通讯作者：
Tsung A