Transcriptional Profiling of Aflatoxin B1-Induced Oxidative Stress and Inflammatory Response in Macrophages.
Transcriptional Profiling of Aflatoxin B1-Induced Oxidative Stress and Inflammatory Response in Macrophages.
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DOI：
10.3390/toxins13060401
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发表时间：
2021-06-04
期刊：
影响因子：
4.2
通讯作者：
Zhao L
中科院分区：
文献类型：
--
作者：
Ma J;Liu Y;Guo Y;Ma Q;Ji C;Zhao L
黄曲霉毒素B1(AFB1)是一种剧毒的真菌毒素，可严重抑制人和动物的免疫系统，并促进活性氧物种(ROS)的形成，导致氧化损伤。然而，AFB1的ROS形成和免疫毒性的机制尚不清楚。这项研究使用了小鼠巨噬细胞RAW264.7细胞系和全转录组测序(RNA-Seq)技术来解决这一知识差距。结果表明，黄曲霉毒素B_1以剂量和时间依赖的方式诱导细胞活力下降。黄曲霉毒素B_1还显著增加细胞内ROS和丙二醛的产生，降低谷胱甘肽水平。这些变化与NOS2、肿瘤坏死因子-α和CXCL2mRNA表达增加，CD86mRNA表达降低有关。通过RNA-Seq技术共鉴定出783个差异表达基因(Deg)。氧化磷酸化途径的KEGG分析显示，AFB1组ND1、ND2、ND3、ND4、ND4L、ND5、ND6、Cytb、COX2、ATPeF0A和ATPeF08的mRNA水平高于对照组，而AFB1组有14个DEGS表达下调。此外，KEGG分析还鉴定了7条由氧化应激介导的免疫调节途径。综上所述，这些数据表明，AFB1通过影响呼吸链诱导巨噬细胞的氧化应激，导致与炎症反应相关的几个信号通路的激活。
Aflatoxin B1 (AFB1) is a highly toxic mycotoxin that causes severe suppression of the immune system of humans and animals, as well as enhances reactive oxygen species (ROS) formation, causing oxidative damage. However, the mechanisms underlying the ROS formation and immunotoxicity of AFB1 are poorly understood. This study used the mouse macrophage RAW264.7 cell line and whole-transcriptome sequencing (RNA-Seq) technology to address this knowledge-gap. The results show that AFB1 induced the decrease of cell viability in a dose- and time-dependent manner. AFB1 also significantly increased intracellular productions of ROS and malondialdehyde and decreased glutathione levels. These changes correlated with increased mRNA expression of NOS2, TNF-α and CXCL2 and decreased expression of CD86. In total, 783 differentially expressed genes (DEGs) were identified via RNA-Seq technology. KEGG analysis of the oxidative phosphorylation pathway revealed that mRNA levels of ND1, ND2, ND3, ND4, ND4L, ND5, ND6, Cyt b, COX2, ATPeF0A and ATPeF08 were higher in AFB1-treated cells than control cells, whereas 14 DEGs were downregulated in the AFB1 group. Furthermore, seven immune regulatory pathways mediated by oxidative stress were identified by KEGG analysis. Altogether, these data suggest that AFB1 induces oxidative stress in macrophages via affecting the respiratory chain, which leads to the activation of several signaling pathways related to the inflammatory response.
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影响因子：
3.6
作者：
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