脱氧雪腐镰刀菌烯醇通过激活 P38 Mapk 和 Erk1/2 诱导 IPEC-J2 细胞炎症。

Deoxynivalenol Induces Inflammation in IPEC-J2 Cells by Activating P38 Mapk And Erk1/2.

机构信息

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.

Jiangsu Vocational College of Agriculture and Forestry, Jurong 212400, China.

出版信息

Toxins (Basel). 2020 Mar 13;12(3):180. doi: 10.3390/toxins12030180.

Fusarium-derived mycotoxin deoxynivalenol (DON) usually induces diarrhea, vomiting and gastrointestinal inflammation. We studied the cytotoxic effect of DON on porcine small intestinal epithelium using the intestinal porcine epithelial cell line IPEC-J2. We screened out differentially expressed genes (DEGs) using RNA-seq and identified 320 upregulated genes and 160 downregulated genes. The enrichment pathways of these DEGs focused on immune-related pathways. DON induced proinflammatory gene expression, including cytokines, chemokines and other inflammation-related genes. DON increased IL1A, IL6 and TNF-α release and DON activated the phosphorylation of extracellular signal-regulated kinase-1 and-2 (ERK1/2), JUN N-terminal kinase (JNK) and p38 MAPK. A p38 inhibitor attenuated DON-induced IL6, TNF-α, CXCL2, CXCL8, IL12A, IL1A, CCL20, CCL4 and IL15 production, while an ERK1/2 inhibitor had only a small inhibitory effect on IL15 and IL6. An inhibitor of p38 MAPK decreased the release of IL1A, IL6 and TNF-α and an inhibitor of ERK1/2 partly attenuated protein levels of IL6. These data demonstrate that DON induces proinflammatory factor production in IPEC-J2 cells by activating p38 and ERK1/2.

镰刀菌来源的真菌毒素脱氧雪腐镰刀菌烯醇（DON）通常会引起腹泻、呕吐和胃肠道炎症。我们使用猪小肠上皮细胞系 IPEC-J2 研究了 DON 对猪小肠上皮的细胞毒性作用。我们使用 RNA-seq 筛选出差异表达基因（DEGs），并鉴定出 320 个上调基因和 160 个下调基因。这些 DEGs 的富集途径主要集中在免疫相关途径上。DON 诱导了促炎基因的表达，包括细胞因子、趋化因子和其他炎症相关基因。DON 增加了 IL1A、IL6 和 TNF-α 的释放，并且 DON 激活了细胞外信号调节激酶-1 和-2（ERK1/2）、JUN N 端激酶（JNK）和 p38 MAPK 的磷酸化。p38 抑制剂减弱了 DON 诱导的 IL6、TNF-α、CXCL2、CXCL8、IL12A、IL1A、CCL20、CCL4 和 IL15 的产生，而 ERK1/2 抑制剂对 IL15 和 IL6 只有很小的抑制作用。p38 MAPK 抑制剂降低了 IL1A、IL6 和 TNF-α 的释放，ERK1/2 抑制剂部分减弱了 IL6 的蛋白水平。这些数据表明 DON 通过激活 p38 和 ERK1/2 诱导 IPEC-J2 细胞中促炎因子的产生。