JNK molecule is a toxic target for IPEC-J2 cell barrier damage induced by T-2 toxin

• Published in: Ecotoxicology and environmental safety Vol. 263; p. 115247
• Main Authors: Chen, Fengjuan, Wang, Youshuang, Chen, Yunhe, Fan, Jiayan, Zhang, Cong, He, Xiuyuan, Yang, Xu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15-09-2023; Elsevier
• Subjects: Inflammation; Intestinal epithelial cells; JNK; T-2 toxin; Tight junction; T-2 toxin; Tight junction; Inflammation; JNK; Intestinal epithelial cells
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2023.115247

The most prevalent contaminated mycotoxin in feed and grain is T-2 toxin. The T-2 toxin's primary action target is the gut because it is the main organ of absorption. T-2 toxin can cause intestinal damage, but, few molecular mechanisms have been elucidated. It is important to discover the key pathways by which T-2 toxin causes enterotoxicity. In this research, IPEC-J2 cells are used as a cell model to investigate the function of the MAPK signaling pathway in T-2 toxin-induced intestinal epithelial cell damage. Throughout this research, T-2 toxin results in functional impairment in IPEC-J2 cells by reducing the TJ proteins Claudin, Occludin-1, ZO-1, N-cadherin, and CX-43 expression. T-2 toxin significantly reduced the survival of IPEC-J2 cells and increased LDH release in a dose-dependent way. T-2 toxin induced IPEC-J2 cell oxidative stress by raising ROS and MDA content, and mitochondrial damage was indicated by a decline in MMP and an increase in the opening degree of MPTP. T-2 toxin upregulated the expression of ERK, P38 and JNK, which triggered the MAPK signaling pathway. In addition, T-2 toxin caused IPEC-J2 cell inflammation responses reflected by increased the levels of inflammation-related factors IL-8, p65, P-p65 and IL-6, and down-regulated IL-10 expression level. Inhibition JNK molecule can ease IPEC-J2 cell functional impairment and inflammatory response. In conclusion, as a consequence of the T-2 toxin activating the JNK molecule, oxidative stress and mitochondrial damage are induced, which impair cellular inflammation.
[Display omitted]
•T-2 toxin induced IPEC-J2 cell mitochondrial damage and oxidative stress.•T-2 toxin caused IPEC-J2 cell dysfunction and inflammation damage.•T-2 toxin induces MAPK signaling pathway activation in IPEC-J2 cells.•T-2 toxin activates the JNK molecule, causing IPEC-J2 cell inflammation.