National 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.
National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China.
Food Chem Toxicol. 2020 Jun;140:111258. doi: 10.1016/j.fct.2020.111258. Epub 2020 Mar 30.
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.
虽然许多研究表明炎症反应在 T-2 毒素的各种毒性作用中起着至关重要的作用，但关于这种现象的机制的报道相对较少。同时，越来越多的证据表明 miR-155-5p 在炎症反应中被激活。由于 T-2 毒素诱导的炎症反应中涉及的分子途径和机制尚未阐明，我们评估了 miR-155-5p 是否参与 T-2 毒素介导的炎症反应。用 T-2 毒素（14 nM 和 12 h）处理 RAW264.7 细胞会导致炎症反应，并伴有 miR-155-5p 基因表达谱的改变。miR-155-5p 的敲低或过表达均表明 miR-155-5p 正向调节炎症因子的表达。此外，生物信息学预测和荧光素酶报告基因实验表明，atg3 和 rheb 是 miR-155-5p 的靶基因。然而，atg3 和 SOCS1 在 miR-155-5p 调节的炎症反应中发挥正作用，而 rheb 则发挥负作用。此外，体内研究表明，T-2 毒素单次给药可增强小鼠脾脏免疫反应，同时 miR-155-5p 表达过度。这些发现表明，miR-155-5p 可能在 T-2 毒素诱导的炎症反应中具有重要作用。总之，揭示了 miR-155-5p 在炎症反应中的双重特性，这可能存在于 miR-155-5p 参与的其他反应中。
