Aflatoxin B1 Induces Reactive Oxygen Species-Mediated Autophagy and Extracellular Trap Formation in Macrophages.
Aflatoxin B1 Induces Reactive Oxygen Species-Mediated Autophagy and Extracellular Trap Formation in Macrophages.
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DOI：
10.3389/fcimb.2017.00053
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发表时间：
2017
影响因子：
5.7
通讯作者：
Yu L
中科院分区：
文献类型：
--
作者：
An Y;Shi X;Tang X;Wang Y;Shen F;Zhang Q;Wang C;Jiang M;Liu M;Yu L
黄曲霉毒素是一组剧毒真菌毒素，具有高致癌性，常见于食品中。黄曲霉毒素B1（AFB 1）是黄曲霉毒素家族中毒性最强的成员。近年来有研究报道黄曲霉毒素B1（AFB 1）可诱导自噬，但AFB 1是否能诱导细胞外陷阱（Extracellular Traps，EAT），以及AFB 1诱导的EAT与天然免疫反应、活性氧（reactive oxygen species，ROS）、自噬之间的关系尚不清楚。本研究证实，黄曲霉毒素B1可诱导巨噬细胞（MΦ）（THP-1细胞和RAW264.7细胞）发生完整的自噬过程。此外，AFB 1还能诱导MΦ β（MET）的产生，并呈剂量依赖性。特别是，MET的形成显著降低了AFB 1的含量。使用特异性抑制剂的进一步分析表明，抑制自噬或ROS可以阻止由AFB 1引起的MET形成，这表明自噬和ROS是AFB 1诱导的MET形成所必需的。ROS的抑制阻止了自噬，表明ROS的产生发生在AFB 1诱导的自噬的上游。综上所述，这些数据表明，AFB 1诱导ROS介导的自噬和巨噬细胞的形成和MΦ中的M1表型。
Aflatoxins are a group of highly toxic mycotoxins with high carcinogenicity that are commonly found in foods. Aflatoxin B1 (AFB1) is the most toxic member of the aflatoxin family. A recent study reported that AFB1 can induce autophagy, but whether AFB1 can induce extracellular traps (ETs) and the relationships among innate immune responses, reactive oxygen species (ROS), and autophagy and the ETs induced by AFB1 remain unknown. Here, we demonstrated that AFB1 induced a complete autophagic process in macrophages (MΦ) (THP-1 cells and RAW264.7 cells). In addition, AFB1 induced the generation of MΦ ETs (METs) in a dose-dependent manner. In particular, the formation of METs significantly reduced the AFB1 content. Further analysis using specific inhibitors showed that the inhibition of either autophagy or ROS prevented MET formation caused by AFB1, indicating that autophagy and ROS were required for AFB1-induced MET formation. The inhibition of ROS prevented autophagy, indicating that ROS generation occurred upstream of AFB1-induced autophagy. Taken together, these data suggest that AFB1 induces ROS-mediated autophagy and ETs formation and an M1 phenotype in MΦ.