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Hydrolyzed Fumonisin B1 induces less inflammatory responses than Fumonisin B1 in the co-culture model of porcine intestinal epithelial and immune cells
Toxicology Letters ( IF 2.9 ) Pub Date : 2019-05-01 , DOI: 10.1016/j.toxlet.2019.01.013 Min Jeong Gu , Seung Eun Han , Kyoryen Hwang , Elisabeth Mayer , Nicole Reisinger , Dian Schatzmayr , Byung-Chul Park , Seung Hyun Han , Cheol-Heui Yun
Toxicology Letters ( IF 2.9 ) Pub Date : 2019-05-01 , DOI: 10.1016/j.toxlet.2019.01.013 Min Jeong Gu , Seung Eun Han , Kyoryen Hwang , Elisabeth Mayer , Nicole Reisinger , Dian Schatzmayr , Byung-Chul Park , Seung Hyun Han , Cheol-Heui Yun
Fumonisin B1 (FB1), mainly produced by Fusarium verticillioides and Fusarium proliferatum, can be converted to the less toxic metabolite hydrolyzed FB1 (HFB1) by enzymatic degradation. The application of an FB1degrading enzyme as a feed additive is a strategy to reduce fumonisin exposure of animals. However, the difference between the effect of FB1 and HFB1 on porcine intestinal immunity is poorly documented. We investigated the toxic effects of FB1 and HFB1 exposure on porcine gut barrier function and intestinal immunity by using a co-culture model of intestinal porcine epithelial cells (IPEC-J2) and porcine peripheral blood mononuclear cells (PBMCs). First, we confirmed that Fusarium mycotoxin (deoxynivalenol; DON), in the presence of an endotoxin (lipopolysaccharide: LPS), disrupted gut permeability of IPEC-J2 and induced inflammatory response in the co-culture system. FB1 induced additional damage to gut barrier function and promoted pro-inflammatory responses in the presence of LPS and DON compared to only LPS/DON treatment. In the co-culture system, FB1/LPS/DON induced increased cell death of PBMCs and pro-inflammatory cytokines than LPS/DON treatment. In contrast, the application of HFB1 resulted in reduced levels of chemokines and pro-inflammatory cytokines together with marginal immune cell death compared to FB1/LPS/DON in the IPEC-J2/PBMC co-culture system. These findings suggest that FB1 aggravates LPS/DON-induced intestinal inflammation, and HFB1 showed less toxicity to immune response. Therefore, enzymatic degradation of FB1 to HFB1 could be an effective strategy to reduce intestinal inflammation in pigs.
中文翻译:
在猪肠上皮和免疫细胞的共培养模型中,水解伏马菌素 B1 比伏马菌素 B1 诱导更少的炎症反应
伏马菌素 B1 (FB1) 主要由轮枝镰孢和增殖镰刀菌产生,可通过酶促降解转化为毒性较小的代谢物水解 FB1 (HFB1)。将 FB1 降解酶用作饲料添加剂是减少动物接触伏马菌素的一种策略。然而,FB1 和 HFB1 对猪肠道免疫的影响之间的差异鲜有记载。我们通过使用猪肠上皮细胞 (IPEC-J2) 和猪外周血单核细胞 (PBMC) 的共培养模型研究了 FB1 和 HFB1 暴露对猪肠道屏障功能和肠道免疫的毒性作用。首先,我们确认镰刀菌毒素(脱氧雪腐镰刀菌烯醇;DON)在内毒素(脂多糖:LPS)存在下,破坏 IPEC-J2 的肠道通透性并在共培养系统中诱导炎症反应。与仅 LPS/DON 治疗相比,在 LPS 和 DON 存在下,FB1 诱导对肠道屏障功能的额外损害并促进促炎反应。在共培养系统中,与 LPS/DON 治疗相比,FB1/LPS/DON 诱导 PBMC 和促炎细胞因子的细胞死亡增加。相比之下,与 IPEC-J2/PBMC 共培养系统中的 FB1/LPS/DON 相比,HFB1 的应用导致趋化因子和促炎细胞因子水平降低以及边缘免疫细胞死亡。这些发现表明 FB1 会加重 LPS/DON 诱导的肠道炎症,而 HFB1 对免疫反应的毒性较小。因此,将 FB1 酶促降解为 HFB1 可能是减少猪肠道炎症的有效策略。
更新日期:2019-05-01
中文翻译:
在猪肠上皮和免疫细胞的共培养模型中,水解伏马菌素 B1 比伏马菌素 B1 诱导更少的炎症反应
伏马菌素 B1 (FB1) 主要由轮枝镰孢和增殖镰刀菌产生,可通过酶促降解转化为毒性较小的代谢物水解 FB1 (HFB1)。将 FB1 降解酶用作饲料添加剂是减少动物接触伏马菌素的一种策略。然而,FB1 和 HFB1 对猪肠道免疫的影响之间的差异鲜有记载。我们通过使用猪肠上皮细胞 (IPEC-J2) 和猪外周血单核细胞 (PBMC) 的共培养模型研究了 FB1 和 HFB1 暴露对猪肠道屏障功能和肠道免疫的毒性作用。首先,我们确认镰刀菌毒素(脱氧雪腐镰刀菌烯醇;DON)在内毒素(脂多糖:LPS)存在下,破坏 IPEC-J2 的肠道通透性并在共培养系统中诱导炎症反应。与仅 LPS/DON 治疗相比,在 LPS 和 DON 存在下,FB1 诱导对肠道屏障功能的额外损害并促进促炎反应。在共培养系统中,与 LPS/DON 治疗相比,FB1/LPS/DON 诱导 PBMC 和促炎细胞因子的细胞死亡增加。相比之下,与 IPEC-J2/PBMC 共培养系统中的 FB1/LPS/DON 相比,HFB1 的应用导致趋化因子和促炎细胞因子水平降低以及边缘免疫细胞死亡。这些发现表明 FB1 会加重 LPS/DON 诱导的肠道炎症,而 HFB1 对免疫反应的毒性较小。因此,将 FB1 酶促降解为 HFB1 可能是减少猪肠道炎症的有效策略。