Cold-inducible RNA-binding protein through TLR4 signaling induces mitochondrial DNA fragmentation and regulates macrophage cell death after trauma.
Cold-inducible RNA-binding protein through TLR4 signaling induces mitochondrial DNA fragmentation and regulates macrophage cell death after trauma.
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冷诱导 RNA 结合蛋白通过 TLR4 信号传导诱导线粒体 DNA 断裂并调节创伤后巨噬细胞死亡
DOI：
10.1038/cddis.2017.187
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发表时间：
2017-05-11
影响因子：
9
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Li Z;Fan EK;Liu J;Scott MJ;Li Y;Li S;Xie W;Billiar TR;Wilson MA;Jiang Y;Wang P;Fan J
创伤是全身炎症反应综合征和多器官功能障碍综合征的主要原因。巨噬细胞（macrophages，M）直接参与创伤诱导的炎症反应，而M的死亡对炎症反应的进展有重要影响。在本研究中，我们探讨了创伤在诱导线粒体DNA（mtDNA）损伤中的重要作用，以及随后对线粒体死亡的调节。使用动物假骨折创伤模型，我们证明了组织损伤诱导NADPH氧化酶活化，并通过冷诱导RNA结合蛋白（CIRP）-TLR 4-MyD 88信号传导增加活性氧的释放。这反过来又激活了内切核酸酶G，它作为线粒体DNA片段化的执行器。我们进一步表明，片段化的mtDNA触发了M细胞中p62相关的自噬和坏死性凋亡。然而，自噬激活也抑制了M细胞坏死性凋亡和促炎反应。这项研究表明，以前未确定的细胞内调节M β稳态响应创伤。
Trauma is a major cause of systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Macrophages (Mϕ) direct trauma-induced inflammation, and Mϕ death critically influences the progression of the inflammatory response. In the current study, we explored an important role of trauma in inducing mitochondrial DNA (mtDNA) damage in Mϕ and the subsequent regulation of Mϕ death. Using an animal pseudo-fracture trauma model, we demonstrated that tissue damage induced NADPH oxidase activation and increased the release of reactive oxygen species via cold-inducible RNA-binding protein (CIRP)–TLR4–MyD88 signaling. This in turn, activates endonuclease G, which serves as an executor for the fragmentation of mtDNA in Mϕ. We further showed that fragmented mtDNA triggered both p62-related autophagy and necroptosis in Mϕ. However, autophagy activation also suppressed Mϕ necroptosis and pro-inflammatory responses. This study demonstrates a previously unidentified intracellular regulation of Mϕ homeostasis in response to trauma.
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DOI：
10.1136/injuryprev-2015-041616
发表时间：
2016-02
期刊：
Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention
影响因子：
--
作者：
Haagsma JA;Graetz N;Bolliger I;Naghavi M;Higashi H;Mullany EC;Abera SF;Abraham JP;Adofo K;Alsharif U;Ameh EA;Ammar W;Antonio CA;Barrero LH;Bekele T;Bose D;Brazinova A;Catalá-López F;Dandona L;Dandona R;Dargan PI;De Leo D;Degenhardt L;Derrett S;Dharmaratne SD;Driscoll TR;Duan L;Petrovich Ermakov S;Farzadfar F;Feigin VL;Franklin RC;Gabbe B;Gosselin RA;Hafezi-Nejad N;Hamadeh RR;Hijar M;Hu G;Jayaraman SP;Jiang G;Khader YS;Khan EA;Krishnaswami S;Kulkarni C;Lecky FE;Leung R;Lunevicius R;Lyons RA;Majdan M;Mason-Jones AJ;Matzopoulos R;Meaney PA;Mekonnen W;Miller TR;Mock CN;Norman RE;Orozco R;Polinder S;Pourmalek F;Rahimi-Movaghar V;Refaat A;Rojas-Rueda D;Roy N;Schwebel DC;Shaheen A;Shahraz S;Skirbekk V;Søreide K;Soshnikov S;Stein DJ;Sykes BL;Tabb KM;Temesgen AM;Tenkorang EY;Theadom AM;Tran BX;Vasankari TJ;Vavilala MS;Vlassov VV;Woldeyohannes SM;Yip P;Yonemoto N;Younis MZ;Yu C;Murray CJ;Vos T
通讯作者：
Vos T
DOI：
10.1038/nri.2016.100
发表时间：
2016-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Cadwell K
通讯作者：
Cadwell K
影响因子：
15.9
作者：
Garcia-Martinez, Irma;Santoro, Nicola;Mehal, Wajahat Zafar
通讯作者：
Mehal, Wajahat Zafar
影响因子：
8
作者：
Higgins, Gavin C.;Beart, Philip M.;Nagley, Phillip
通讯作者：
Nagley, Phillip
影响因子：
29
作者：
Leadsham, Jane E.;Sanders, Geraldine;Gourlay, Campbell W.
通讯作者：
Gourlay, Campbell W.