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棕榈果生物活性成分可在体外调节人星形胶质细胞活性,改变细胞因子分泌谱,降低 TNFα、RANTES 和 IP-10 的水平。

Palm Fruit Bioactives modulate human astrocyte activity in vitro altering the cytokine secretome reducing levels of TNFα, RANTES and IP-10.

机构信息

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Biomaterials Science and Engineering Laboratory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

出版信息

Sci Rep. 2018 Nov 6;8(1):16423. doi: 10.1038/s41598-018-34763-3.

Abstract

Neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, are becoming more prevalent and an increasing burden on society. Neurodegenerative diseases often arise in the milieu of neuro-inflammation of the brain. Reactive astrocytes are key regulators in the development of neuro-inflammation. This study describes the effects of Palm Fruit Bioactives (PFB) on the behavior of human astrocytes which have been activated by IL-1β. When activated, the astrocytes proliferate, release numerous cytokines/chemokines including TNFα, RANTES (CCL5), IP-10 (CXCL10), generate reactive oxygen species (ROS), and express specific cell surface biomarkers such as the Intercellular Adhesion Molecule (ICAM), Vascular Cellular Adhesion Molecule (VCAM) and the Neuronal Cellular Adhesion Molecule (NCAM). Interleukin 1-beta (IL-1β) causes activation of human astrocytes with marked upregulation of pro-inflammatory genes. We show significant inhibition of these pro-inflammatory processes when IL-1β-activated astrocytes are exposed to PFB. PFB causes a dose-dependent and time-dependent reduction in specific cytokines: TNFα, RANTES, and IP-10. We also show that PFB significantly reduces ROS production by IL-1β-activated astrocytes. Furthermore, PFB also reduces the expression of ICAM and VCAM, both in activated and naïve human astrocytes in vitro. Since reactive astrocytes play an essential role in the neuroinflammatory state preceding neurodegenerative diseases, this study suggests that PFB may have a potential role in their prevention and/or treatment.

摘要

神经退行性疾病,包括阿尔茨海默病和帕金森病,变得越来越普遍,给社会带来了越来越大的负担。神经退行性疾病通常发生在大脑神经炎症的环境中。反应性星形胶质细胞是神经炎症发展的关键调节因子。本研究描述了棕榈果生物活性物质(PFB)对被白细胞介素 1β(IL-1β)激活的人星形胶质细胞行为的影响。当被激活时,星形胶质细胞增殖,释放包括 TNFα、RANTES(CCL5)、IP-10(CXCL10)在内的多种细胞因子/趋化因子,产生活性氧物质(ROS),并表达特定的细胞表面标志物,如细胞间黏附分子(ICAM)、血管细胞黏附分子(VCAM)和神经元细胞黏附分子(NCAM)。白细胞介素 1β(IL-1β)导致人星形胶质细胞激活,促炎基因显著上调。当 IL-1β 激活的星形胶质细胞暴露于 PFB 时,我们显示出这些促炎过程的显著抑制。PFB 导致特定细胞因子:TNFα、RANTES 和 IP-10 的剂量依赖性和时间依赖性减少。我们还表明,PFB 显著降低了 IL-1β 激活的星形胶质细胞产生的 ROS。此外,PFB 还降低了体外激活和未激活的人星形胶质细胞中 ICAM 和 VCAM 的表达。由于反应性星形胶质细胞在神经退行性疾病之前的神经炎症状态中发挥着重要作用,因此本研究表明,PFB 可能在其预防和/或治疗中具有潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e4e/6219577/9bf08bf04659/41598_2018_34763_Fig1_HTML.jpg

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