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Human Microglial Cells Undergo Proapoptotic Induction and Inflammatory Activation upon in vitro Exposure to a Naturally Occurring Level of Aflatoxin B1.
Neuroimmunomodulation ( IF 2.2 ) Pub Date : 2018-10-20 , DOI: 10.1159/000493528
Jalil Mehrzad 1 , Saman Hosseinkhani 2 , Amir Mohammad Malvandi 3
Affiliation  

OBJECTIVE Knowledge regarding interactions of AFB1 with the human nervous system and how a naturally occurring level of AFB1 could potentially induce neuroimmune dysregulation is very limited. To assess the cellular effects of AFB1 on the human brain, we used the human microglia cell line CHME5 as a model to pinpoint its potential in vivo translation. METHODS We used the CHME5 cell line culture system, multiplex qPCR, (chemi)bioluminescence, Luminex ELISA, and flow cytometry assays to evaluate the toxic effects of a naturally occurring level of AFB1 on human microglia. RESULTS A low concentration of AFB1 upregulates the mRNA expression of many proinflammatory molecules, such as TLRs, MyD88, NFκB, and CxCr4, induces intracellular ATP depletion, and increases caspase-3/7 activity at different time points following exposure to the toxin. Furthermore, AFB1-exposed microglia secreted significantly higher levels of IFN-γ and GM-CSF after treatment. We also observed a slight increase in the percentage of apoptotic microglia (annexin V+/PI-) at 48 h posttreatment. CONCLUSION Our work confirmed that the environmentally relevant level of AFB1 could cause an inflammatory reaction in human microglial cells that is potentially harmful or toxic to the homeostasis of the human central nervous system and might increase susceptibility to neurodegenerative diseases.

中文翻译:

在体外暴露于自然发生水平的黄曲霉毒素B1后,人类小胶质细胞经历促凋亡和炎症激活。

目的关于AFB1与人类神经系统的相互作用以及AFB1的天然水平如何可能引起神经免疫失调的知识非常有限。为了评估AFB1对人脑的细胞作用,我们使用人小胶质细胞系CHME5作为模型来确定其潜在的体内翻译。方法我们使用CHME5细胞系培养系统,多重qPCR,(化学)生物发光,Luminex ELISA和流式细胞术测定来评估AFB1天然存在水平对人小胶质细胞的毒性作用。结果低浓度的AFB1会上调许多促炎分子(如TLRs,MyD88,NFκB和CxCr4)的mRNA表达,诱导细胞内ATP消耗,并在暴露于毒素后的不同时间点增加caspase-3 / 7活性。此外,治疗后,暴露于AFB1的小胶质细胞分泌的IFN-γ和GM-CSF水平明显升高。我们还观察到在治疗后48小时,凋亡小胶质细胞(膜联蛋白V + / PI-)的百分比略有增加。结论我们的工作证实,与环境有关的AFB1含量可能会引起人类小胶质细胞发炎反应,对人类中枢神经系统的稳态具有潜在的危害或毒性,并可能增加对神经退行性疾病的敏感性。
更新日期:2019-11-01
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