Immunotoxicity of ochratoxin A and aflatoxin B1 in combination is associated with the nuclear factor kappa B signaling pathway in 3D4/21 cells
Immunotoxicity of ochratoxin A and aflatoxin B1 in combination is associated with the nuclear factor kappa B signaling pathway in 3D4/21 cells
复制标题
赭曲霉毒素 A 和黄曲霉毒素 B1 组合的免疫毒性与 3D4/21 细胞中的核因子 kappa B 信号通路相关。
DOI：
10.1016/j.chemosphere.2018.02.009
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发表时间：
2018-05-01
期刊：
影响因子：
8.8
通讯作者：
Huang, Kehe
中科院分区：
文献类型：
--
作者：
Hou, Lili;Gan, Fang;Huang, Kehe
霉菌毒素对谷物、谷物、农作物和动物饲料的共污染是一个普遍性问题。人类和动物同时暴露于几种真菌毒素，这一点已被广泛的研究所证实。然而，大多数研究都单独讨论了霉菌毒素的影响。黄曲霉毒素B1和赭曲霉毒素A可引起免疫毒性。然而，目前尚不清楚这些真菌毒素的组合是否会增强免疫毒性以及这种作用的潜在机制。本研究利用猪肺泡巨噬细胞、天然免疫细胞和细胞系3D 4/21进行了体外培养。结果表明，与对照组相比，不同浓度的黄曲霉毒素B1和赭曲霉毒素A联合作用后，细胞抑制率、膜联蛋白V/PI阳性率、促炎细胞因子（肿瘤坏死因子α和白细胞介素-6）的表达均显著增加，乳酸脱氢酶的释放和吞噬指数均显著降低。黄曲霉毒素B1和赭曲霉毒素A的组合显着降低GSH的产生和增加活性氧水平。而N-乙酰半胱氨酸可抑制氧化应激，减轻联合用药引起的免疫毒性。黄曲霉毒素B1和赭曲霉毒素A的组合显着增强I κ Ba的降解，核因子κ B（p65）的磷酸化，并通过蛋白质印迹和共聚焦激光扫描显微镜证实活化的核因子κ B（NF-κ B B）的易位到细胞核中。这些作用可被NF-κ B的特异性抑制剂BAY 11-7082逆转。总之，黄曲霉毒素B1和赭曲霉毒素A的组合可以通过激活NF-κ B信号通路来加重免疫毒性。(C)2018爱思唯尔有限公司版权所有
The co-contamination of cereals, grains, crops, and animal feeds by mycotoxins is a universal problem. Humans and animals are exposed to several mycotoxins simultaneously as evidenced by extensive studies on this topic. Yet, most studies have addressed the effects of mycotoxins individually. Aflatoxin B1 and ochratoxin A can induce immunotoxicity. However, it remains unclear whether a combination of these mycotoxins aggravates immunotoxicity and the potential mechanism underlying this effect. In this study, we used the cell line 3D4/21, swine alveolus macrophages and innate immune cell. The results showed that the percentage of cell inhibition, annexin V/Pl-positive rates, and the expression of pro inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) significantly increased and the release of lactate dehydrogenase and phagocytotic index were significantly decreased at different concentrations of aflatoxin B1 and ochratoxin A combination when compared with control. The combination of aflatoxin B1 and ochratoxin A significantly decreased the production of GSH and increased reactive oxygen species level. However, N-acetylcysteine suppressed the oxidative'stress and alleviated the immunotoxicity induced by the combination. The combination of aflatoxin B1 and ochratoxin A markedly enhanced the degradation of I kappa Ba, the phosphorylation of nuclear factor kappa B (p65), and the translocation of activated nuclear factor kappa B (NF-kappa B) into the nuclei as demonstrated by western blotting and confocal laser scanning microscopy. These effects could be reversed by BAY 11-7082, a specific inhibitor of NF-kappa B. Taken together, a combination of aflatoxin B1 and ochratoxin A could aggravate immunotoxicity by activating the NF-kappa B signaling pathway. (C) 2018 Elsevier Ltd. All rights reserved.