Activation of inflammasomes requires intracellular redistribution of the apoptotic speck-like protein containing a caspase recruitment domain.
Activation of inflammasomes requires intracellular redistribution of the apoptotic speck-like protein containing a caspase recruitment domain.
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DOI：
10.4049/jimmunol.0802367
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发表时间：
2009-03-01
期刊：
影响因子：
--
通讯作者：
Stehlik C
中科院分区：
文献类型：
--
作者：
Bryan NB;Dorfleutner A;Rojanasakul Y;Stehlik C
半胱天冬酶-1的激活对于白细胞介素（IL）-1β和IL-18的成熟和释放至关重要，并且发生在多蛋白复合物中，称为炎性小体。含有半胱天冬酶募集结构域（ASC）的凋亡相关斑点样蛋白是将半胱天冬酶原-1募集到炎性小体中的必需衔接蛋白，并且ASC的一致基因消融消除了半胱天冬酶-1活化和IL-1β和IL-18的分泌。然而，内源性ASC的分布尚未得到详细研究。在本研究中，我们证明，ASC主要定位于细胞核在休息的人单核细胞巨噬细胞。在病原体感染后，ASC迅速重新分布到胞质溶胶中，随后是核周聚集体的组装，其含有几种炎性小体组分，包括半胱天冬酶-1和Nod样受体（NLR）。预防ASC胞浆再分布完全消除病原体诱导的炎性体活性，这证实ASC的胞浆定位对于炎性体功能是必需的。因此，我们的研究特征的一种新的机制，炎症调节宿主防御。
Activation of caspase-1 is essential for the maturation and release of interleukin (IL)-1β and IL-18, and occurs in multi-protein complexes, referred to as inflammasomes. The apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is the essential adaptor protein for recruiting pro-caspase-1 into inflammasomes, and consistently gene ablation of ASC abolishes caspase-1 activation and secretion of IL-1β and IL-18. However, distribution of endogenous ASC has not yet been examined in detail. In the present study we demonstrated that ASC localized primarily to the nucleus in resting human monocytes macrophages. Upon pathogen infection ASC rapidly redistributed to the cytosol, followed by assembly of perinuclear aggregates, containing several inflammasome components, including caspase-1 and Nod-like receptors (NLRs). Prevention of ASC cytosolic redistribution completely abolished pathogen induced inflammasome activity, which affirmed that cytosolic localization of ASC is essential for inflammasome function. Thus, our study characterized a novel mechanism of inflammasome regulation in host defense.
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影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
DOI：
10.1073/pnas.0611496104
发表时间：
2007-05-08
影响因子：
11.1
作者：
Duncan, Joseph A.;Bergstralht, Daniel T.;Ting, Jenny Pan-Yun
通讯作者：
Ting, Jenny Pan-Yun
影响因子：
3.1
作者：
Dorfleutner, Andrea;Bryan, Nicole B.;Stehlik, Christian
通讯作者：
Stehlik, Christian
影响因子：
158.5
作者：
Jin, Ying;Mailloux, Christina M.;Spritz, Richard A.
通讯作者：
Spritz, Richard A.
影响因子：
9.2
作者：
Feldmeyer, Laurence;Keller, Martin;Beer, Hans-Dietmar
通讯作者：
Beer, Hans-Dietmar