The mycotoxin fumonisin B1 alters the proliferation and the barrier function of porcine intestinal epithelial cells
The mycotoxin fumonisin B1 alters the proliferation and the barrier function of porcine intestinal epithelial cells
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DOI：
10.1093/toxsci/kfh006
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发表时间：
2004-01-01
影响因子：
3.8
通讯作者：
Oswald, IP
中科院分区：
文献类型：
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作者：
Bouhet, S;Hourcade, E;Oswald, IP
伏马菌素B-1 （FB1）是由一种通常污染玉米的真菌——黄萎病镰刀菌（原念珠菌）产生的真菌毒素。FB1对实验室和包括猪在内的家畜产生毒理学效应。由于胃肠道是外源食物化合物遇到的第一道屏障，因此本研究的目的是研究FB1对猪肠上皮细胞系IPEC-1的影响。我们首先证实低浓度的FB1对IPEC-1没有任何细胞毒性作用。事实上，只有FB1浓度分别大于50和700 muM时，增殖细胞和非增殖细胞才有显著的LDH释放。然后我们证明了FB1抑制IPEC-1的增殖。细胞周期的荧光活化细胞分选（FACS）分析表明，FB1在G0/G1期阻断肠细胞的增殖。用肾猪上皮细胞系LLC-PK1获得了类似的结果，被认为是研究FB1体外作用的良好模型。我们还评估了FB1对肠上皮形成屏障完整性的影响。我们证明了FB1以时间和剂量依赖的方式降低IPEC-1的经上皮电阻（TEER）。这种效果只有在长时间暴露（治疗8-12天）后才会注意到。FB1诱导TEER降低与细胞分化阶段无关，且该作用部分可逆。综上所述，我们的数据表明，FB1改变了肠细胞的增殖和屏障功能。这些结果可能对食用受fb1污染的食品或饲料的人类和动物产生影响。
Fumonisin B-1 (FB1) is a mycotoxin produced by Fusarium verticillioides (formerly F. moniliforme), a fungus that commonly contaminates maize. FB1 causes toxicological effects in laboratory and domestic animals including pigs. Because the gastrointestinal tract represents the first barrier met by exogenous food compounds, the purpose of this study was to investigate the effects of FB1 on IPEC-1, a porcine intestinal epithelial cell line. We first verified that low concentrations of FB1 did not exert any cytotoxic effect on IPEC-1. Indeed, significant LDH release was only observed for FB1 concentrations greater than 50 and 700 muM on proliferating and nonproliferating cells, respectively. We then demonstrated that FB1 inhibits proliferation of IPEC-1. Fluorescence-activated cell sorting (FACS) analysis of the cell cycle indicated that FB1 blocks the proliferation of intestinal cells in the G0/G1 phase. Similar results were obtained with LLC-PK1, a renal porcine epithelial cell line, which is considered to be a good model for studying FB1 in vitro effects. We have also assessed the effects of FB1 on the integrity of the barrier formed by the intestinal epithelium. We demonstrated that FB1 decreases the transepithelial electrical resistance (TEER) of IPEC-1 in a time- and dose-dependent manner. This effect was only noticed after a long exposure (8-12 days of treatment). FB1 induced the TEER decrease independently of the cell differentiation stage, and this effect was partially reversible. Taken together, our data indicate that FB1 alters the proliferation and the barrier function of intestinal cells. These results may have implications for humans and animals consuming FB1-contaminated food or feed.