School of Biological Sciences, Faculty of Science, Kadoorie Biological Sciences Building, The University of Hong Kong, Pokfulam, Hong Kong.
Toxicol Lett. 2013 Jul 18;220(3):238-46. doi: 10.1016/j.toxlet.2013.05.003. Epub 2013 May 17.
Fusarium toxins have been arousing public interest in recent years because of their potential health hazards for humans and agricultural livestock. It was hypothesized that selected pro-inflammatory cytokines might serve as sensitive biomarkers of the predicted adverse effects of Fusarium toxins on the basis of their potential ability to induce immune and intestinal alterations comparable to those in human chronic inflammatory infection. Consequently, the aim of this study was to elucidate individual and combined effects of four common Fusarium toxins, deoxynivalenol (DON), nivalenol (NIV), zearalenone (ZEA) and fumonisin B1 (FB1) on the mRNA expression of pro-inflammatory cytokines (IL1α, IL1β, IL6, IL8, TNFα and MCP-1) using a porcine jejunal epithelial cell line, IPEC-J2. Based on a dose-response relationship between individual mycotoxins and cell viability (MTT assay) that was previously established, cytotoxic and non-cytotoxic concentrations were selected to investigate combinations of two, three and all four of the mycotoxins. In general, up-regulation of pro-inflammatory cytokine mRNA expression occurred for both individual and mixtures of Fusarium toxins at cytotoxic concentrations, whereas significant up-regulation of pro-inflammatory cytokine mRNA mostly obtained when the toxins existed in mixtures at non-cytotoxic concentrations and these mixtures were found to cause cytotoxicity from MTT assay determined previously. Therefore, it may be concluded that some of the changes in the mRNA expression of IL1α, IL1β, IL6, IL8, TNFα and MCP-1 could be cytotoxicity-related. It was also noted that additive effects were not always observed for the mixtures. These data suggest that individual or mixtures of Fusarium toxins could cause or exacerbate intestinal inflammation. These also provide a better understanding of the possible effects of Fusarium toxins, alone or in combinations on the immunological defense mechanisms of IECs, which would contribute to the risk assessment of these toxins.
近年来，由于镰刀菌毒素可能对人类和农业牲畜的健康造成危害，因此引起了公众的关注。有人假设，某些促炎细胞因子可能成为镰刀菌毒素对预测的不利影响的敏感生物标志物，这是基于它们潜在的诱导免疫和肠道改变的能力与人类慢性炎症感染相当。因此，本研究旨在使用猪小肠上皮细胞系 IPEC-J2 阐明四种常见镰刀菌毒素（脱氧雪腐镰刀菌烯醇（DON）、雪腐镰刀菌烯醇（NIV）、玉米赤霉烯酮（ZEA）和伏马菌素 B1（FB1））对促炎细胞因子（IL1α、IL1β、IL6、IL8、TNFα 和 MCP-1）的 mRNA 表达的单独和联合作用。基于先前建立的单个霉菌毒素与细胞活力（MTT 测定）之间的剂量-反应关系，选择细胞毒性和非细胞毒性浓度来研究两种、三种和四种霉菌毒素的组合。一般来说，在细胞毒性浓度下，单独和混合物的镰刀菌毒素都会引起促炎细胞因子 mRNA 的上调，而当毒素在非细胞毒性浓度下以混合物形式存在并且这些混合物在先前确定的 MTT 测定中导致细胞毒性时，大多数促炎细胞因子 mRNA 的上调显著。因此，可以得出结论，IL1α、IL1β、IL6、IL8、TNFα 和 MCP-1 的 mRNA 表达的一些变化可能与细胞毒性有关。还注意到，混合物并不总是表现出相加作用。这些数据表明，单独或混合物的镰刀菌毒素可能会导致或加剧肠道炎症。这些也提供了对镰刀菌毒素单独或组合对 IEC 免疫防御机制可能产生的影响的更好理解，这将有助于这些毒素的风险评估。
