Aflatoxin B1 Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway
Aflatoxin B1 Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway
复制标题
黄曲霉毒素 B1 抑制原代猪脾细胞中抗猪 CD3 单克隆抗体刺激的 T 细胞反应：细胞外调节蛋白激酶 (ERK1/2) MAPK 信号通路的作用。
DOI：
10.1021/acs.jafc.5b00433
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发表时间：
2015-07-08
影响因子：
6.1
通讯作者：
Huang, Kehe
中科院分区：
文献类型：
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作者：
Hao, Shu;Pan, Shengchi;Huang, Kehe
本研究的目的是探讨黄曲霉毒素 B1 (AFB1) 诱导的免疫毒性是否与氧化应激和细胞外调节蛋白激酶 (ERK) 1/2 的表达相关。在本实验中，从健康猪中分离出的原代脾细胞被抗猪CD3单克隆抗体（mAb）激活并增殖，该抗体是一种抗原特异性兴奋剂。结果表明，与对照组相比，4 至 8 μg/mL 的 AFB1 显着抑制细胞增殖和白介素 2 (IL-2) 产生，且呈剂量依赖性。此外，AFB1 显着增加丙二醛 (MDA) 水平，降低还原型谷胱甘肽 (GSH) 和总超氧化物歧化酶水平，并上调活化脾细胞中 p-ERK1/2 的表达。 N-乙酰-l-半胱氨酸分别通过增加细胞内 GSH 浓度、降低 MDA 水平和下调 p-ERK1/2 表达来阻断 AFB1 引起的抗 CD3 诱导的 T 细胞抑制。 ERK 特异性 iRNA 对 ERK1/2 表达的抑制减弱了 AFB1 诱导的 T 细胞增殖和 IL-2 产生的减少。结论是AFB1通过氧化应激介导的ERK1/2 MAPK信号通路抑制抗CD3诱导的淋巴细胞增殖和IL-2产生。
The aim of the present study is to investigate whether aflatoxin B1 (AFB1)-induced immunotoxicity is associated with oxidative stress and the expression of extracellular regulated protein kinases (ERK) 1/2. The primary splenocytes isolated from healthy pigs were activated and proliferated by anti-pig-CD3 monoclonal antibodies (mAb) in the present experiment, which is an antigen-specific stimulant. Results indicated that cell proliferation and interleukin-2 (IL-2) production were significantly suppressed by AFB1 from 4 to 8 μg/mL in a dose-dependent manner compared to the control group. Furthermore, AFB1 significantly increased malondialdehyde (MDA) levels, decreased reduced glutathione (GSH) and total superoxide dismutase levels, and up-regulated p-ERK1/2 expression in the activated splenocytes. N-Acetyl-l-cysteine blocked anti-CD3-induced T-cell suppression by AFB1 through increasing intracellular concentrations of GSH levels, decreasing MDA levels, and down-regulated p-ERK1/2 expression, respectively. Inhibition of the ERK1/2 expression by ERK-specific iRNA attenuated the decrease of T-cell proliferation and IL-2 production induced by AFB1. It was concluded that AFB1 inhibits anti-CD3-induced lymphocyte proliferation and IL-2 production by the oxidative stress mediated ERK1/2 MAPK signaling pathway.