NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes.
NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes.
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DOI：
10.1371/journal.pone.0130624
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Dostert C
中科院分区：
文献类型：
--
作者：
Gustin A;Kirchmeyer M;Koncina E;Felten P;Losciuto S;Heurtaux T;Tardivel A;Heuschling P;Dostert C
神经炎症是大脑对感染、创伤、有毒分子或蛋白质聚集体的局部反应。脑内巨噬细胞、小胶质细胞能够触发适当的反应，包括细胞因子和趋化因子的分泌，导致星形胶质细胞的活化和外周免疫细胞的募集。IL-1β在这种反应中发挥着重要作用;但其在大脑中的产生和作用方式尚未完全了解，其在神经退行性疾病中的确切含义需要进一步表征。我们的研究结果表明，形成功能性NLRP 3炎性小体和分泌IL-1β的能力仅限于小鼠脑中的小胶质细胞区室。我们不能观察到星形胶质细胞分泌IL-1β，它们也不表达所有的NLRP 3炎性体组分。小胶质细胞能够响应于不同的经典炎性体激活剂（如ATP、白细胞介素或明矾）而产生IL-1β。同样，小胶质细胞分泌IL-18和IL-1α，这两种其他炎性小体相关的促炎因子。用α-突触核蛋白（一种神经退行性疾病相关肽）刺激细胞不会导致小胶质细胞释放活性IL-1β，尽管其促炎作用较弱。β淀粉样蛋白肽能够激活小胶质细胞中的NLRP 3炎性小体，并且IL-1β的分泌以P2 X7受体非依赖性方式发生。因此，小胶质细胞依赖性炎性小体活化可以在脑中，特别是在神经炎性病症中发挥重要作用。
Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response involving secretion of cytokines and chemokines, resulting in the activation of astrocytes and recruitment of peripheral immune cells. IL-1β plays an important role in this response; yet its production and mode of action in the brain are not fully understood and its precise implication in neurodegenerative diseases needs further characterization. Our results indicate that the capacity to form a functional NLRP3 inflammasome and secretion of IL-1β is limited to the microglial compartment in the mouse brain. We were not able to observe IL-1β secretion from astrocytes, nor do they express all NLRP3 inflammasome components. Microglia were able to produce IL-1β in response to different classical inflammasome activators, such as ATP, Nigericin or Alum. Similarly, microglia secreted IL-18 and IL-1α, two other inflammasome-linked pro-inflammatory factors. Cell stimulation with α-synuclein, a neurodegenerative disease-related peptide, did not result in the release of active IL-1β by microglia, despite a weak pro-inflammatory effect. Amyloid-β peptides were able to activate the NLRP3 inflammasome in microglia and IL-1β secretion occurred in a P2X7 receptor-independent manner. Thus microglia-dependent inflammasome activation can play an important role in the brain and especially in neuroinflammatory conditions.
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影响因子：
3.7
作者：
Freeman D;Cedillos R;Choyke S;Lukic Z;McGuire K;Marvin S;Burrage AM;Sudholt S;Rana A;O'Connor C;Wiethoff CM;Campbell EM
通讯作者：
Campbell EM
影响因子：
64.8
作者：
通讯作者：
--
CD36介导了对β-淀粉样蛋白的先天宿主反应。
影响因子：
15.3
作者：
El Khoury, JB;Moore, KJ;Means, TK;Leung, J;Terada, K;Toft, M;Freeman, MW;Luster, AD
通讯作者：
Luster, AD
影响因子：
16.8
作者：
Hanamsagar R;Hanke ML;Kielian T
通讯作者：
Kielian T
影响因子：
4.7
作者：
Hanamsagar R;Torres V;Kielian T
通讯作者：
Kielian T