Although many studies have shown that inflammatory response plays a crucial role in the various toxic effects of T-2 toxin, there are relatively few reports on the mechanism of this phenomenon. Meanwhile, accumulating evidence has shown that miR-155-5p is activated in the inflammatory response. As molecular pathways and mechanisms involved in T-2 toxin-induced inflammatory response are poorly elucidated, we assessed whether miR-155-5p is involved in the inflammation effects mediated by T-2 toxin. Treatment of RAW264.7 cells with T-2 toxin (14 nM and 12 h) resulted in inflammatory response and associated with alteration of the gene expression signature of miR-155-5p. Knockdown or overexpression of miR-155-5p both indicated that miR-155-5p positively regulated the expression of the inflammation factors. Moreover, bioinformatics prediction and luciferase assay indicated that atg3 and rheb are targets of miR-155-5p. However, atg3 and SOCS1 play positive roles in the inflammatory response regulated by miR-155-5p, while rheb plays a negative role. In addition, the in vivo study showed that single administration of T-2 toxin in mice enhances spleen immune response, which was accompanied by an overexpression of miR-155-5p. These findings indicate that miR-155-5p might have an important role associated with the inflammatory response induced by T-2 toxin. In conclusion, a dual character of miR-155-5p in inflammation response was revealed, which might exist in other reactions in which miR-155-5p is involved.

• MeSH
• Cytokines metabolism   MeSH
• Inflammation Mediators metabolism   MeSH
• MicroRNAs metabolism   MeSH
• Mice MeSH
• RAW 264.7 Cells MeSH
• Signal Transduction MeSH
• T-2 Toxin MeSH
• Up-Regulation MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

T-2 toxin is a secondary metabolite produced by Fusarium species and commonly contaminates food and animal feed. T-2 toxin can induce hepatotoxicity through apoptosis and oxidative stress; however, the underlying mechanism is not clear. Recent studies indicated that RASSF4, a member of the RASSF family, participates in cell apoptosis and some cancers due to its inactivation via DNA hypermethylation. However, its role in T-2 toxin-induced liver toxicity is poorly understood. Therefore, in this study, female Wistar rats were given a single dose of T-2 toxin at 2 mg/kg b.w. and were sacrificed at 1, 3 and 7 days post-exposure. A normal rat liver cell line (BRL) was exposed to different concentrations of T-2 toxin (10, 20, 40 nM) for 4, 8, 12 h, respectively. Histopathological analysis revealed with apoptosis in some liver cells and clear proliferation under T-2 toxin exposure. Expression analysis by immunohistochemical assays, quantitative real-time PCR (qPCR) and western blot demonstrated that T-2 toxin activated PI3K-Akt/Caspase/NF-κB signaling pathways. Additionally, DNA methylation assays revealed that the expression of RASSF4 was silenced by promoter hypermethylation after exposure to T-2 toxin for 1 and 3 days as compared to the control group. Moreover, joint treatment of 5-Aza-2'-deoxycytidine (DAC) (5 μM) and T-2 toxin (40 nM) increased expression of RASSF4 and PI3K-Akt/caspase/NF-κB signaling pathways-related genes, inducing cell apoptosis. These findings for the first time demonstrated that DNA methylation regulated the RASSF4 expression under T-2 toxin, along with the activation of its downstream pathways, resulting in apoptosis.

• MeSH
• Apoptosis drug effects   MeSH
• Cell Line MeSH
• Intracellular Signaling Peptides and Proteins metabolism   MeSH
• Liver drug effects   metabolism   MeSH
• Rats MeSH
• Real-Time Polymerase Chain Reaction MeSH
• DNA Methylation * drug effects   MeSH
• Tumor Suppressor Proteins metabolism   MeSH
• Rats, Wistar MeSH
• Flow Cytometry MeSH
• T-2 Toxin toxicity   MeSH
• Dose-Response Relationship, Drug MeSH
• Blotting, Western MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH