MicroRNA-223Regulates VSV-induced TypeⅠ Interferon By Targeting NLRP3in Mocrophage

Interferons(IFNs) are cytokines that are spontaneously produce in response to virus infection. Induction of type I interferon is a central event of innate immunity, essential for host defense.MiRNAs, the new-found endogenous noncoding RNAs non-coding RNAs, in addition to the transcriptional control of gene expression, in recent years it was recognized that microRNA-mediated posttran-scriptional regulation plays another important role in controlling gene expression. miR-223was previously shown to be a myeloid-specific miRNA. However, whether miR-223is involved in regulating the production of type-I interferon and its target need to be further demonstrated.In our study, in mouse macrophage cell line RAW264.7and peritoneal macrophages, miR-223treated with VSV showed significant down-regulation. We used miR-223mimics and the result showed that miR-223could increase IFN-α, IFN-βproduction in VSV-infected macrophages but not TNF-α, IL-6. Over-expression of miR-223in RAW264.7cells,then we used VSV-GFP infect the cells,the date of Laser-scanning confocal and microscopy flow cytometer show the VSV infected cells decrease. As miRNAs exerts its biological effects through posttranscriptional inhibition of their target genes, miR-223exerts its immune modulatory function probably through directly targeting NLRP3expression. Over-expression of NLRP3markedly decreased the luciferase activity expression of IRF3and IFN-β, suggests that NLRP3negatively regulates type I IFN production.In conclusion, we found that miR-223can increase the production of IFN α, IFN-β by inhibiting NLRP3in macrophages after VSV infection.The study is to reveal the function of the non-coding RNA of regulating the innate immune response in macrophage provides a theoretical basis, and the diagnosis and treatment of infectious diseases may provide potential targets and ideas.