Impact of T-2 toxin on intestinal inflammation and transcriptional regulation of inflammatory response in mouse macrophages.

T-2 toxin, a fungal secondary metabolite produced by toxigenic species, poses a significant threat to grain food and feed due to its potential to cause intestinal inflammation in livestock and poultry. Macrophages play a crucial role as integral components of the body's immune system during intestinal inflammation. This study aimed to elucidate the mechanism behind the inflammatory response triggered by T-2 toxin in macrophages. Compared to the control group, gavage administration of T-2 toxin (0.33, 1, and 4 mg kg) led to a decrease in body weight and feed intake, along with histopathological alterations in the colon of mice. In addition, T-2 toxin induced the upregulation of macrophage-derived cytokines like IL-1β, IL-6, and TNF-α, as well as a rise in the population of F4/80 macrophages in the colon. T-2 toxin also led to the upregulation of IL-1β, IL-6, and TNF-α in mouse bone marrow-derived macrophages (BMDMs). Furthermore, the transcriptomic analysis of BMDMs exposed to T-2 toxin (10 nM) identified the "TNF signaling pathway," "Lipid and atherosclerosis," "Epstein-Barr virus infection," "MAPK signaling pathway," and the "NF-kappa B signaling pathway" as the top five significantly enriched pathways. Subsequently, twelve inflammation-related genes were randomly chosen for validation through quantitative reverse transcription PCR (RT-qPCR), with the results corroborating those from the transcriptomic analysis. The comprehensive analysis of transcriptome data highlights the activation of several signaling pathways associated with the inflammatory response following T-2 toxin-induced BMDMs, offering potential therapeutic targets for the prevention and treatment of T-2 toxin-induced intestinal inflammation.