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Published on: January 7, 2019
MiR-155-5p plays as a "janus" in the expression of inflammatory cytokines induced by T-2 toxin
Pu Guo1, Fang Qiao2, Deyu Huang3
1National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Abstract:
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.
Insights
MicroRNA-155-5p plays a dual role in T-2 toxin-induced inflammation, acting as a positive regulator through atg3 and SOCS1, but a negative regulator via rheb. This study elucidates miR-155-5p
Area of Science:
- Toxicology
- Molecular Biology
- Immunology
Background:
- T-2 toxin induces inflammatory responses, but the underlying mechanisms are not fully understood.
- MicroRNA-155-5p (miR-155-5p) is known to be activated during inflammation.
Purpose of the Study:
- To investigate the role of miR-155-5p in T-2 toxin-induced inflammatory responses.
- To elucidate the molecular mechanisms by which miR-155-5p mediates inflammation.
Main Methods:
- Treatment of RAW264.7 cells with T-2 toxin.
- Knockdown and overexpression of miR-155-5p.
- Bioinformatics prediction and luciferase assays to identify miR-155-5p targets.
- In vivo studies in mice.
Main Results:
- T-2 toxin exposure induced inflammatory responses and altered miR-155-5p expression in cells.
- miR-155-5p positively regulated inflammation factors.
- atg3 and SOCS1 were identified as positive regulators, while rheb was a negative regulator of miR-155-5p-mediated inflammation.
- T-2 toxin administration in mice increased spleen immune response and miR-155-5p expression.
Conclusions:
- miR-155-5p is involved in T-2 toxin-induced inflammation.
- miR-155-5p exhibits a dual role in regulating inflammatory responses.
- The findings suggest miR-155-5p as a potential therapeutic target for T-2 toxin-related inflammatory conditions.
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