This study investigated the immunotoxic effects of the mycotoxin nivalenol (NIV) using antigen-presenting cells and a mouse model of atopic dermatitis (AD). In vitro experiments were conducted using a mouse macrophage cell line (RAW 264.7) and mouse dendritic cell line (DC 2.4). After cells were exposed to NIV (0.19–5 µmol) for 24 h, the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) was quantified. To further investigate the inflammatory cytokine production pathway, the possible involvement of mitogen-activated protein kinase (MAPK) pathways, such as ERK1/2, p-38, and JNK, in NIV exposure was analyzed using MAPK inhibitors and phosphorylation analyses. In addition, the pro-inflammatory effects of oral exposure to NIV at low concentrations (1 or 5 ppm) were evaluated in an NC/Nga mouse model of hapten-induced AD. In vitro experiments demonstrated that exposure to NIV significantly enhanced the production of TNFα. In addition, it also directly induced the phosphorylation of MAPK, indicated by the inhibition of TNFα production following pretreatment with MAPK inhibitors. Oral exposure to NIV significantly exacerbated the symptoms of AD, including a significant increase in helper T cells and IgE-produced B cells in auricular lymph nodes and secretion of pro-inflammatory cytokines, such as IL-4, IL-5, and IL-13, compared with the vehicle control group. Our findings indicate that exposure to NIV directly enhanced the phosphorylation of ERK1/2, p-38, and JNK, resulting in a significant increase in TNFα production in antigen-presenting cells, which is closely related to the development of atopic dermatitis.

本研究使用抗原呈递细胞和特应性皮炎 (AD) 小鼠模型研究了霉菌毒素雪腐镰刀菌烯醇 (NIV) 的免疫毒性作用。使用小鼠巨噬细胞系（RAW 264.7）和小鼠树突状细胞系（DC 2.4）进行体外实验。将细胞暴露于 NIV (0.19–5 µmol) 24 小时后，对促炎细胞因子（IL-1β、IL-6 和 TNFα）的产生进行定量。为了进一步研究炎症细胞因子的产生途径，使用 MAPK 抑制剂和磷酸化分析分析了丝裂原激活蛋白激酶 (MAPK) 途径（例如 ERK1/2、p-38 和 JNK）在 NIV 暴露中可能的参与。此外，在半抗原诱导的 AD NC/Nga 小鼠模型中评估了口服低浓度（1 或 5 ppm）NIV 的促炎作用。体外实验表明，暴露于 NIV 显着增强了 TNFα 的产生。此外，它还直接诱导 MAPK 的磷酸化，这可以通过 MAPK 抑制剂预处理后抑制 TNFα 的产生来证明。口服 NIV 显着加剧 AD 症状，包括耳廓淋巴结中辅助 T 细胞和 IgE 产生的 B 细胞显着增加，以及促炎细胞因子（如 IL-4、IL-5 和 IL-4）的分泌。 13、与媒介物对照组相比。我们的研究结果表明，暴露于NIV直接增强了ERK1/2、p-38和JNK的磷酸化，导致抗原呈递细胞中TNFα的产生显着增加，这与特应性皮炎的发生密切相关。