Surfactin inducing mitochondria-dependent ROS to activate MAPKs, NF-κB and inflammasomes in macrophages for adjuvant activity.
Surfactin inducing mitochondria-dependent ROS to activate MAPKs, NF-κB and inflammasomes in macrophages for adjuvant activity.
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表面活性素诱导线粒体依赖性 ROS 激活巨噬细胞中的 MAPK、NF-κB 和炎症小体，从而发挥佐剂活性
DOI：
10.1038/srep39303
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发表时间：
2016-12-14
影响因子：
4.6
通讯作者：
Qi G
中科院分区：
文献类型：
--
作者：
Gan P;Gao Z;Zhao X;Qi G
表面活性素是一种天然脂肽，可作为胃肠外和非胃肠外佐剂用于引发免疫应答。然而，赋予其佐剂特性的机制尚未完全探索。用NHS-罗丹明B标记的surfactin和Mito-Tracker绿色染色，发现surfactin可穿透巨噬细胞与线粒体结合，诱导活性氧产生，而活性氧抑制剂则可抑制活性氧的产生。ROS可促进巨噬细胞NF-κB核转位后p38 MAPK和JNK的表达及其磷酸化，而ROS抑制剂可明显抑制NF-κB核转位。然而，抑制ROS的产生只减弱了p38 MAPK和JNK的表达，而不是它们的磷酸化在巨噬细胞。结果表明，表面活性剂可激活NF-κB，通过ROS信号通路释放TNF-α。ROS还诱导巨噬细胞凋亡，释放内源性危险信号，在体外激活NLRP 1，NLRP 3，IPAF和AIM 2的炎性小体，在体内仅激活NLRP 1，以及巨噬细胞中的caspase-1和IL-1，这些都被ROS抑制剂预处理显著抑制。总之，表面活性素作为一种非病原体相关的分子模式，通过多种信号通路调节宿主的天然免疫，包括诱导依赖于ROS的活性氧，激活MAPK和NF-κB，诱导细胞凋亡释放内源性危险信号，激活炎性小体。
Surfactin, a natural lipopeptide, can be used both as parenteral and non-parenteral adjuvant for eliciting immune response. However, the mechanisms that confer its adjuvant properties have not been fully explored. By staining with NHS-Rhodamine B labeled surfactin and Mito-Tracker Green, we found surfactin could penetrate into macrophages to bind with mitochondria, following induce ROS that could be inhibited by mitochondria-dependent ROS inhibitor. ROS enhanced p38 MAPK and JNK expression, as well their phorsphorylation, following activated NF-κB nuclear translocation in macrophages that was obviously inhibited by mitochondria-dependent ROS inhibitor. However, inhibition of ROS production only weakened p38 MAPK and JNK expression, but not their phosphorylation in macrophages. As a result, surfaction could activate NF-κB to release TNF-α by the mitochondria-dependent ROS signalling pathway. ROS also induced macrophages apoptosis to release endogenous danger signals, following activated inflammasomes of NLRP1, NLRP3, IPAF and AIM2 in vitro and only NLRP1 in vivo, as well caspase-1 and IL-1 in macrophages, which were significantly inhibited by pre-treatment with ROS inhibitors. Collectively, surfactin as a kind of non-pathogen-associated molecular patterns, modulates host innate immunity by multiple signalling pathways, including induction of mitochondria-dependent ROS, activating MAPKs and NF-κB, and inducing cell apoptosis to realease endogenous danger signals for activation of inflammasomes.
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影响因子：
5.5
作者：
Cain, Derek W.;Sanders, Sergio E.;Cunningham, Michael M.;Kelsoe, Garnett
通讯作者：
Kelsoe, Garnett
影响因子：
5.6
作者：
Park, Sun Young;Kim, YoungHee
通讯作者：
Kim, YoungHee
影响因子：
7.4
作者：
Ahlemeyer, B;Bauerbach, E;Krieglstein, J
通讯作者：
Krieglstein, J
影响因子：
3
作者：
Qi Gaofu;Zhu Fayin;Zhao Xiuyun
通讯作者：
Zhao Xiuyun
DOI：
10.1006/bbrc.1998.9678
发表时间：
1998-11-18
影响因子：
3.1
作者：
Marrero, MB;Venema, VJ;Venema, RC
通讯作者：
Venema, RC