Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Drug Chem Toxicol. 2021 Jan;44(1):39-46. doi: 10.1080/01480545.2018.1556682. Epub 2019 Feb 11.
Aflatoxin M (AFM) is a 4-hydroxylated metabolite of aflatoxin B (AFB). It induces various toxicological effects including immunotoxicity. In the present study, we investigated the effects of AFM on immune system and its modulation by MicroRNA (miR)-155. AFM was administered intraperitoneally at doses of 25 and 50 µg/kg for 28 days to Balb/c mice and different immune system parameters were analyzed. The levels of miR-155 and targeted proteins were evaluated in isolated T cells from spleens of mice. Spleen weight was reduced in mice exposed to AFM compared to negative control. Proliferation of splenocytes in response to phytohemagglutinin-A was reduced in mice exposed to AFM. IFN-γ was decreased in mice exposed to AFM, whereas IL-10 was increased. Concentration of IL-4 did not change different in mice exposed to AFM compared to negative control. Exposure to AFM reduced the expression of miR-155. Significant upregulation of phosphatidylinositol-3, 4, 5-trisphosphate 5-phosphatase 1 (Ship1) and suppressor of cytokine signaling 1 (Socs1) was observed in isolated T cells from spleens of mice treated with AFM but the transcription factor Maf (c-MAF) was not affected. These results suggest that miR-155 and targeted proteins might be involved in the immunotoxicity observed in mice exposed to AFM.
黄曲霉毒素 M（AFM）是黄曲霉毒素 B（AFB）的 4-羟基化代谢物。它会引起各种毒理学效应，包括免疫毒性。在本研究中，我们研究了 AFM 对免疫系统的影响及其对 MicroRNA（miR）-155 的调节作用。AFM 以 25 和 50μg/kg 的剂量腹腔注射到 Balb/c 小鼠体内，28 天后分析不同的免疫系统参数。评估了从小鼠脾脏中分离的 T 细胞中 miR-155 和靶向蛋白的水平。与阴性对照组相比，暴露于 AFM 的小鼠脾脏重量减轻。暴露于 AFM 的小鼠脾细胞对植物血凝素 A 的增殖反应减少。IFN-γ在暴露于 AFM 的小鼠中减少，而 IL-10 增加。与阴性对照组相比，暴露于 AFM 的小鼠 IL-4 浓度没有变化。AFM 暴露降低了 miR-155 的表达。在暴露于 AFM 的小鼠脾脏中分离的 T 细胞中观察到磷脂酰肌醇-3,4,5-三磷酸 5-磷酸酶 1（Ship1）和细胞因子信号转导抑制因子 1（Socs1）的显著上调，但转录因子 Maf（c-MAF）不受影响。这些结果表明，miR-155 和靶向蛋白可能参与了暴露于 AFM 的小鼠的免疫毒性。
