From Inflammasome to Exosome-Does Extracellular Vesicle Secretion Constitute an Inflammasome-Dependent Immune Response?
From Inflammasome to Exosome-Does Extracellular Vesicle Secretion Constitute an Inflammasome-Dependent Immune Response?
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从炎性小体到外泌体——细胞外囊泡分泌是否构成炎性小体依赖的免疫反应？
DOI：
10.3389/fimmu.2018.02188
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发表时间：
2018
影响因子：
7.3
通讯作者：
Matikainen S
中科院分区：
文献类型：
--
作者：
Cypryk W;Nyman TA;Matikainen S
炎性小体是由模式识别受体和caspase-1组成的细胞内蛋白质复合体，在调节巨噬细胞和树突状细胞的炎症反应中具有重要作用。炎性小体的主要作用是催化促炎细胞因子IL-1、β和IL-18的加工和分泌。最近，由caspase-4/5激活的细胞内非典型炎性小体被阐明，caspase-4/5也是通过处理Gasdermin D而调节下垂的。Caspase-1是炎症体复合体的效应蛋白，也被认为可以调节大量其他蛋白质的分泌。因此，除了在处理促炎细胞因子方面的已知作用外，炎症体还成为蛋白质分泌的通用调节器，允许暴露在危险中的细胞释放各种蛋白质，以警示和引导邻近细胞。这些蛋白中的大多数不是通过传统的ER-高尔基体分泌途径分泌的。取而代之的是，它们被隔离在膜封闭的隔间里，并分泌在纳米级的细胞外小泡中，这些小泡保护它们的货物并引导它们运送。越来越多的证据表明，炎性小体的活动与细胞外小泡的分泌增加和蛋白质含量的调节有关。这种炎症体驱动的非常规、囊泡介导的多种免疫调节蛋白的分泌可能构成炎症反应的新范式。在这篇简短的综述中，我们讨论了目前的知识，并强调了关于代谢过程、信号和将炎症体活动与调节细胞外蛋白质囊泡分泌联系起来的机制的未解决的问题。对这种关系的进一步研究未来可能有助于理解细胞外囊泡分泌在炎症性疾病中的重要性，如动脉粥样硬化、痛风性关节炎、哮喘、阿尔茨海默氏症和许多其他疾病。
Inflammasomes are intracellular protein complexes of pattern recognition receptors and caspase-1, with essential functions in regulating inflammatory responses of macrophages and dendritic cells. The primary role of inflammasomes is to catalyze processing and secretion of pro-inflammatory cytokines IL-1β and IL-18. Recently, intracellular non-canonical inflammasome activation by caspases-4/5, which are also regulators of pyroptosis via processing gasdermin D, has been elucidated. Caspase-1, the effector protease of inflammasome complex, is also known to modulate secretion of large number of other proteins. Thereby, besides its known role in processing pro-inflammatory cytokines, the inflammasome turns into a universal regulator of protein secretion, which allows the danger-exposed cells to release various proteins in order to alert and guide neighboring cells. Majority of these proteins are not secreted through the conventional ER-Golgi secretory pathway. Instead, they are segregated in membrane-enclosed compartment and secreted in nanosized extracellular vesicles, which protect their cargo and guide it for delivery. Growing evidence indicates that inflammasome activity correlates with enhanced secretion of extracellular vesicles and modulation of their protein cargo. This inflammasome-driven unconventional, vesicle-mediated secretion of multitude of immunoregulatory proteins may constitute a novel paradigm in inflammatory responses. In this mini review we discuss the current knowledge and highlight unsolved questions about metabolic processes, signals, and mechanisms linking inflammasome activity with regulated extracellular vesicle secretion of proteins. Further investigations on this relationship may in the future help understanding the significance of extracellular vesicle secretion in inflammatory diseases such as atherosclerosis, gouty arthritis, asthma, Alzheimer's and many others.
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形成孔的蛋白质加油D可以调节白细胞介素-1的巨噬细胞分泌。
影响因子：
32.4
作者：
Evavold CL;Ruan J;Tan Y;Xia S;Wu H;Kagan JC
通讯作者：
Kagan JC
巨噬细胞激活和极化改变 P2X7 受体分泌组，影响炎症过程。
影响因子：
4.6
作者：
de Torre-Minguela C;Barberà-Cremades M;Gómez AI;Martín-Sánchez F;Pelegrín P
通讯作者：
Pelegrín P
影响因子：
7.3
作者：
Iula L;Keitelman IA;Sabbione F;Fuentes F;Guzman M;Galletti JG;Gerber PP;Ostrowski M;Geffner JR;Jancic CC;Trevani AS
通讯作者：
Trevani AS
影响因子：
4.4
作者：
Kankkunen, Paivi;Teirila, Laura;Matikainen, Sampsa
通讯作者：
Matikainen, Sampsa
链球菌为链球菌激活NLRP3炎症体需要链霉菌素O和NF-kappa B激活，但与TLR信号传导和P2X7受体无关进行。
DOI：
10.4049/jimmunol.0900444
发表时间：
2009-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Harder J;Franchi L;Muñoz-Planillo R;Park JH;Reimer T;Núñez G
通讯作者：
Núñez G