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衰老牛脑中的自噬与 NLRP3 炎性小体在神经炎症中的相互作用。

Autophagy and NLRP3 inflammasome crosstalk in neuroinflammation in aged bovine brains.

机构信息

Department of Veterinary Medicine and Animal Production, University of Naples "Federico II", Naples, Italy.

Department of Translational Medicine, University of Naples "Federico II", Naples, Italy.

出版信息

J Cell Physiol. 2020 Jun;235(6):5394-5403. doi: 10.1002/jcp.29426. Epub 2020 Jan 5.

DOI:10.1002/jcp.29426
PMID:31903559
Abstract

NLRP3 inflammasome is a multiprotein complex that can sense several stimuli such as autophagy dysregulation and increased reactive oxygen species production stimulating inflammation by priming the maturation of proinflammatory cytokines interleukin-1β and interleukin-18 in their active form. In the aging brain, these cytokines can mediate the innate immunity response priming microglial activation. Here, we describe the results of immunohistochemical and molecular analysis carried out on bovine brains. Our results support the hypothesis that the age-related impairment in cellular housekeeping mechanisms and the increased oxidative stress can trigger the inflammatory danger sensor NLRP3. Moreover, according to the recent scientific literature, we demonstrate the presence of an age-related proinflammatory environment in aged brains consisting in an upregulation of interleukin-1β, an increased microglial activation and increased NLRP3 expression. Finally, we suggest that bovine may potentially be a pivotal animal model for brain aging studies.

摘要

NLRP3 炎性小体是一种多蛋白复合物,能够感知多种刺激,如自噬失调和活性氧产生增加,通过激活前炎性细胞因子白细胞介素-1β和白细胞介素-18 的成熟来刺激炎症。在衰老的大脑中,这些细胞因子可以介导先天免疫反应,激活小胶质细胞。在这里,我们描述了对牛脑进行的免疫组织化学和分子分析的结果。我们的结果支持这样一种假设,即与年龄相关的细胞管家机制的损伤和氧化应激的增加会触发炎症危险传感器 NLRP3。此外,根据最近的科学文献,我们证明了衰老大脑中存在与年龄相关的促炎环境,表现为白细胞介素-1β的上调、小胶质细胞激活的增加和 NLRP3 表达的增加。最后,我们建议牛可能是研究大脑衰老的关键动物模型。

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