School of Veterinary Medicine, Laboratory of Veterinary Pharmacology, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa, 252-5201, Japan.
Bioalch Co., Ltd., 3-28 Honshuku-cho, Fuchu, Tokyo, Japan.
Arch Toxicol. 2023 Oct;97(10):2707-2719. doi: 10.1007/s00204-023-03579-0. Epub 2023 Aug 17.
Contamination with fumonisins produced by Fusarium spp. is rapidly growing in both developing and developed countries. The purpose of this study was to determine whether oral exposure to fumonisin contributed to the development of allergic diseases. We initially examined the immunotoxic potential of short-term, oral administration of fumonisin B1 (FB1, 1 mg/kg) and fumonisin B2 (FB2, 1 mg/kg), both naturally occurring fumonisins, using a BALB/c mouse model of allergic contact dermatitis and Dermatophagoides farina-induced asthma. Using an NC/nga mouse model of atopic dermatitis (AD), we evaluated the adverse effects of subchronic oral exposure to low concentrations of FB2 (2 or 200 μg/kg). Finally, we explored the influence of FB2 on regulatory T cell proliferation and function in mesenteric lymph nodes after 1-week oral exposure to FB2 in BALB/c mice. Oral exposure to FB2 markedly exacerbated the symptoms of allergy, including skin thickness, histological evaluation, immunocyte proliferation, and proinflammatory cytokine production, although no change was observed following exposure to FB1. Furthermore, oral exposure to low concentrations of FB2 considerably exacerbated the AD scores, skin thickness, transepidermal water loss, histological features, and proinflammatory cytokine production. The aggravated allergic symptoms induced by oral exposure to FB2 could be attributed to the direct inhibition of IL-10 production by regulatory T cells in mesenteric lymph nodes. Our findings indicate that the recommended maximum fumonisin level should be reconsidered based on the potential for allergy development.
在发展中国家和发达国家,由镰刀菌属( Fusarium spp. )产生的伏马菌素污染都在迅速增加。本研究的目的是确定口服暴露于伏马菌素是否会导致过敏性疾病的发生。我们最初使用过敏性接触性皮炎的 BALB/c 小鼠模型和粉尘螨诱导的哮喘模型,检测了短期口服给予天然伏马菌素 FB1(1mg/kg)和 FB2(1mg/kg)的免疫毒性。在 NC/nga 特应性皮炎(AD)小鼠模型中,我们评估了低浓度 FB2(2 或 200μg/kg)亚慢性口服暴露的不良影响。最后,我们探索了在 BALB/c 小鼠中 FB2 对肠道淋巴结中调节性 T 细胞增殖和功能的影响,方法是在 FB2 口服暴露 1 周后。口服 FB2 明显加重了过敏症状,包括皮肤厚度、组织学评估、免疫细胞增殖和促炎细胞因子产生,尽管 FB1 暴露后没有观察到变化。此外,口服低浓度 FB2 可显著加重 AD 评分、皮肤厚度、经皮水分丢失、组织学特征和促炎细胞因子产生。口服 FB2 引起的过敏症状加重可能归因于肠道淋巴结中调节性 T 细胞 IL-10 产生的直接抑制。我们的研究结果表明,应根据过敏发展的可能性重新考虑推荐的最大伏马菌素水平。