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

• Published in: Toxins 2020-03, Vol.12 (3), p.180
• Main Authors: Zhang, Hua, Deng, Xiwen, Zhou, Chuang, Wu, Wenda, Zhang, Haibin
• Format: Article
• Language: English
• Subjects: Animals; Carbon tetrachloride; CCL20 protein; CCL4 protein; Cell Line; Cell Survival - drug effects; Chemokines; Cytokines; Cytotoxicity; Deoxynivalenol; Diarrhea; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelium; Extracellular signal-regulated kinase; Food contamination & poisoning; Gene expression; Genes; Health aspects; Inflammation; Inhibitors; Interleukin 1; Interleukin 15; Interleukin 6; Interleukin-1 - genetics; Interleukin-6 - genetics; Intestinal Mucosa - drug effects; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestine; ipec-j2 cells; Kinases; MAP kinase; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - genetics; MAP Kinase Signaling System - immunology; mapks; Mitogen-activated protein kinases; Mycotoxins; Oxidative stress; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Proteins; Ribonucleic acid; RNA; rna-seq; Studies; Swine; Transcriptome - drug effects; Trichothecenes - toxicity; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-α; Vomiting
• ISSN: 2072-6651; 2072-6651
• 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.