Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome.
Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome.
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作者：
自噬是细胞器和蛋白质周转的细胞过程，调节先天免疫反应。我们证明，自噬蛋白微管相关蛋白-1轻链3B（LC 3B）和Beclin 1的耗竭增强了caspase-1的激活和白细胞介素-1 β和白细胞介素-18的分泌。自噬蛋白耗竭可促进巨噬细胞内脂多糖（LPS）和ATP引起的功能障碍性线粒体的积聚和线粒体DNA（mtDNA）的胞浆转位。线粒体DNA释放到细胞质中依赖于NALP 3炎性体和线粒体ROS。胞浆mtDNA参与LPS和ATP刺激下IL-1β和IL-18的分泌。在两种脓毒症模型中，LC 3B缺陷小鼠产生更多的caspase-1依赖性细胞因子，并且对LPS诱导的死亡率敏感。我们的研究表明，自噬蛋白通过保持线粒体的完整性来调节NALP 3依赖性炎症。
Autophagy, a cellular process for organelle and protein turnover, regulates innate immune responses. We demonstrate that depletion of autophagic proteins microtubule associated protein-1 light chain 3B (LC3B) and Beclin 1 enhances caspase-1 activation and secretion of interleukin-1β and interleukin-18. Autophagic protein depletion promoted accumulation of dysfunctional mitochondria and cytosolic translocation of mitochondrial DNA (mtDNA) in response to lipopolysaccharide (LPS) and ATP in macrophages. Release of mtDNA into the cytosol depended on the NALP3 inflammasome and mitochondrial ROS. Cytosolic mtDNA contributed to IL-1β and IL-18 secretion in response to LPS and ATP. LC3B-deficient mice produced more caspase-1-dependent cytokines in two sepsis models and were susceptible to LPS-induced mortality. Our study suggests that autophagic proteins regulate NALP3-dependent inflammation by preserving mitochondrial integrity.
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影响因子：
11.1
作者：
He C;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
4.8
作者：
Li, NY;Ragheb, K;Robinson, JP
通讯作者：
Robinson, JP
DOI：
10.1164/rccm.200703-418oc
发表时间：
2008-05-01
影响因子：
24.7
作者：
Fahy, Ruairi J.;Exline, Matthew C.;Wewers, Mark D.
通讯作者：
Wewers, Mark D.
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.5
作者：
Garcia-Marcos, M;Fontanils, U;Marino, A
通讯作者：
Marino, A