LOX-1 - dependent mitochondrial DNA damage and NLRP3 activation during systemic inflammation in mice.
LOX-1 - dependent mitochondrial DNA damage and NLRP3 activation during systemic inflammation in mice.
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DOI：
10.1016/j.bbrc.2014.08.034
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发表时间：
2014-09
影响因子：
3.1
通讯作者：
Zufeng Ding;Shijie Liu;Xianwei Wang;S. Theus;Yubo Fan;Xiaoyan Deng;J. Mehta
中科院分区：
文献类型：
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作者：
Zufeng Ding;Shijie Liu;Xianwei Wang;S. Theus;Yubo Fan;Xiaoyan Deng;J. Mehta
背景凝集素样氧化低密度脂蛋白清道夫受体-1（LOX-1）参与了许多病理生理学事件，如炎症。方法为了阐明LOX-1在线粒体DNA损伤和NLRP 3炎性小体激活中的作用，我们研究了给予巯基乙酸盐的野生型（WT）和LOX-1敲除（KO）小鼠，结果我们观察到强烈的炎症反应（CD 45和CD 68表达）和线粒体DNA损伤的WT小鼠脾和肾巯基乙酸。消除LOX-1（使用LOX-1敲除小鼠）减少了炎症反应以及mtDNA损伤（与WT小鼠相比P< 0.05）。我们还观察到LOX-1缺失的小鼠的caspase-1（P10和P20亚基）表达以及裂解的IL-1β和IL-18显著降低。这些小鼠也有少得多的线粒体DNA损伤和只有有限的NLRP 3炎性体expression.ConclusionsThesein体内观察表明，LOX-1在线粒体DNA损伤，然后导致炎症过程中NLRP 3炎性体激活起着关键作用。
BackgroundLectin-like oxidized low-density lipoprotein scavenger receptor-1 (LOX-1) is known to be involved in many pathophysiological events, such as inflammation.MethodsTo clarify the role of LOX-1 in mtDNA damage and NLRP3 inflammasome activation, we studied wild-type (WT) and LOX-1 knockout (KO) mice given thioglycollate, an inflammatory stimulus.ResultsWe observed intense inflammatory response (CD45 and CD68 expression) and mtDNA damage in spleen and kidneys of WT mice given thioglycollate. The abrogation of LOX-1 (use of LOX-1 knockout mice) reduced the inflammatory response as well as mtDNA damage (P< 0.05 vs. WT mice). We also observed that mice with LOX-1 deletion had markedly reduced expression of caspase-1 (P10 and P20 subunits) as well as cleaved IL-1β and IL-18. These mice also had much less mtDNA damage and only limited NLRP3 inflammasome expression.ConclusionsThesein vivoobservations indicate that LOX-1 plays a key role in mtDNA damage which then leads to NLRP3 inflammasome activation during inflammation.