Bouhet Sandrine, Hourcade Edith, Loiseau Nicolas, Fikry Asmaa, Martinez Stephanie, Roselli Marianna, Galtier Pierre, Mengheri Elena, Oswald Isabelle P
Laboratoire de Pharmacologie-Toxicologie, Institut National de Recherche Agronomique, 31931 Toulouse, France.
Toxicol Sci. 2004 Jan;77(1):165-71. doi: 10.1093/toxsci/kfh006. Epub 2003 Nov 4.
Fumonisin B1 (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 microM 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.
伏马菌素B1（FB1）是由轮枝镰孢菌（以前称为串珠镰孢菌）产生的一种霉菌毒素，该真菌通常会污染玉米。FB1会对包括猪在内的实验动物和家畜产生毒理学影响。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调查FB1对猪小肠上皮细胞系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，仅在增殖细胞和非增殖细胞中，分别当FB1浓度大于50和700微摩尔时，才观察到显著的乳酸脱氢酶释放。然后我们证明FB1抑制IPEC-1的增殖。细胞周期的荧光激活细胞分选（FACS）分析表明，FB1在G0/G1期阻断肠道细胞的增殖。用猪肾上皮细胞系LLC-PK1也得到了类似的结果，该细胞系被认为是体外研究FB1作用的良好模型。我们还评估了FB1对肠上皮形成的屏障完整性的影响。我们证明FB1以时间和剂量依赖性方式降低IPEC-1的跨上皮电阻（TEER）。这种作用仅在长时间暴露（治疗8 - 12天）后才被注意到。FB1诱导TEER降低与细胞分化阶段无关，并且这种作用部分是可逆的。综上所述，我们的数据表明FB1改变了肠道细胞的增殖和屏障功能。这些结果可能对食用受FB1污染的食物或饲料的人类和动物有影响。
