AUTHOR=Wang Shiqi , Peng Xiaoxu , Zhu Qi , Lu Sichen , Hu Ping , Kim In Ho , Liu Hao-Yu , Ennab Wael , Muniyappan Madesh , Cai Demin 

TITLE=Lithocholic acid attenuates DON-induced inflammatory responses via epigenetic regulation of DUSP5 and TRAF5 in porcine intestinal epithelial cells

JOURNAL=Frontiers in Veterinary Science

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2025.1493496

DOI=10.3389/fvets.2025.1493496

ISSN=2297-1769

ABSTRACT=Deoxynivalenol (DON) is the most common mycotoxin that frequently contaminates human food and animal feed, resulting in intestinal diseases and systemic immunosuppression. Lithocholic acid (LCA) exhibits various pharmacological activities. RNA-seq and ChIP-qPCR analysis were used in the current study to investigate the protective mechanism of LCA for DON-induced inflammatory Responses via Epigenetic Regulation of DUSP5 and TRAF5 in porcine ileal epithelial cell lines (IPI-2I) cells. The IPI-2I cells were treated with the vehicle group, 250 ng/mL DON, 20 μmol/L LCA, 250 ng/mL DON+ 20 μmol/L LCA for 24 h could induce inflammatory Responses via Epigenetic Regulation of DUSP5 and TRAF5 in IPI-2I cells. By analyzing the transcriptional profiles of DON and LCA-treated IPI-2I, we observed significant transcriptional changes in IPI-2I cells. Further analysis of up-and down-regulated differential genes revealed the enrichment of pathways closely related to inflammation and apoptosis, such as the MAPK signaling pathway, IL17 signaling pathway, and Wnt signaling pathway. An upregulated (p < 0.05) relative mRNA expression level of RAP1B, GDNF, FGF2, IL1R1, RAPGEF2, DUSP5, TGFB3, CACNA1G, TEK and RPS6KA2 were noted in IPI-2I exposed to DON. DON-exposed IPI-2I cells dramatically enhanced (p < 0.05) histone marks associated with transcriptional activation, H3K9ac, H3K18ac, H3K27ac, H3K4me1, H3K9bhb, H3K18bhb Pol-II and Ser5 Pol-II at the enhancers of DUSP5 and TRAF5. Overall, our findings provide a theoretical basis for understanding the mechanism of action of LCA in attenuating DON-induced intestinal injury and for better understanding the potential of LCA as a treatment or prevention of mycotoxin-associated intestinal diseases in swine production.