Discipline of Medical Biochemistry, School of Laboratory of Medicine and Medical Sciences, College of Health Science, University of KwaZulu-Natal, Durban, South Africa.
Sci Rep. 2017 Jun 8;7(1):3051. doi: 10.1038/s41598-017-03183-0.
Fusaric acid (FA), a food-borne mycotoxin, is a potent divalent metal chelator. The human immune system is complex and susceptible to environmental insult however, the immunotoxity of FA remains unknown. We investigated the immunotoxicity of FA on human peripheral blood mononuclear cells (PBMCs) and Thp-1 cells. FA was cytotoxic to PBMCs (IC-240.8 μg/ml) and Thp-1 (IC-107.7 μg/ml) cells at 24 h. FA induced early apoptosis but significantly decreased caspase activity in PBMCs, a characteristic of paraptosis. In Thp-1 cells, FA induced apoptosis and increased caspase -9 and -3/7 activities. In PBMCs, FA maintained mitochondrial membrane potential and decreased protein expression of Bax whilst increasing expression of p-Bcl-2; FA induced oxidative stress and depleted ATP levels in both cell types. In Thp-1 cells, FA increased mitochondrial membrane depolarization and decreased p-Bcl-2 expression. In PBMCs, FA significantly up-regulated the MAPK protein expression of p-ERK and p-JNK but down-regulated p-p38 expression. In Thp-1 cells, FA up-regulated MAPK protein expression of p-ERK whilst p-JNK and p-p38 expression were down-regulated. In conclusion FA induced programmed cell death and altered MAPK signaling in healthy PBMCs and Thp-1 cells strongly suggesting a possible mechanism of FA induced immunotoxicity in vitro.
伏马菌素（FA）是一种食源性真菌毒素，是一种有效的二价金属螯合剂。人体免疫系统复杂，易受环境刺激影响，但 FA 的免疫毒性仍不清楚。我们研究了 FA 对人外周血单核细胞（PBMCs）和 Thp-1 细胞的免疫毒性。FA 在 24 小时时对 PBMCs（IC-240.8μg/ml）和 Thp-1（IC-107.7μg/ml）细胞具有细胞毒性。FA 诱导 PBMCs 早期凋亡，但显著降低半胱天冬酶活性，这是 Paraptosis 的特征。在 Thp-1 细胞中，FA 诱导凋亡并增加半胱天冬酶 -9 和 -3/7 活性。在 PBMCs 中，FA 维持线粒体膜电位，降低 Bax 蛋白表达，同时增加 p-Bcl-2 表达；FA 诱导氧化应激并耗尽两种细胞类型的 ATP 水平。在 Thp-1 细胞中，FA 增加线粒体膜去极化并降低 p-Bcl-2 表达。在 PBMCs 中，FA 显著上调 p-ERK 和 p-JNK 的 MAPK 蛋白表达，但下调 p-p38 表达。在 Thp-1 细胞中，FA 上调 p-ERK 的 MAPK 蛋白表达，而 p-JNK 和 p-p38 表达下调。总之，FA 诱导健康 PBMCs 和 Thp-1 细胞程序性细胞死亡并改变 MAPK 信号通路，这强烈表明 FA 诱导的免疫毒性的体外可能机制。
