The Molecule Mechanism Of MiR-22 Modulates Type ? Interferon And Inflammatory Cytokines Production

Micro RNAs(miRNAs)are critical regulators of gene expression that utilize sequence complementarity to bind to and decrease the stability or translatio n efficiency of target mRNAs.Recent studies have revealed that miRN As widely participate not only in cell proliferation,differentiation,apoptosis and organogenesis,but also play an important role in innate immunity and viral infection.The activation o f the innate immunity and viral infection can modulate miRNA expression,which can employ feedback mechanism to regulate innate immunity and viral infection.Poly(I:C)is a double-stranded RN A immunostimulant,which can be sensed by cellular innate immune receptor and induce type I interferon and inflammatory cytokines production.In our study,we investigated the expression level of miR-22 of poly(I:C)and JEV(Japanese encephalitis virus)treated astrocytes as well as the molecule mechanism of mir-22 modulates type I interferon and inflammatory cytokines production during the process.The main contents were described as follows:1.miR-22 is upregulated in poly(I:C)-treated cellsmiR-22 expression level upon poly(I:C)treated U251 cells and SH-SY5 Y cells were determined by quantitative real-time PC R.The results revealed miR-22 expression was significantly up-regulated in a time and dose-dependent manner.2.miR-22 negatively regulates poly(I:C)-triggered type I interferon and inflammatory cytokine productionOverexpression of miR-22 signifcantly decreased poly(I:C)-triggered IFN-? production and inflammatory cytokines,whereas inhibition of miR-22 expression increased poly(I:C)-triggered IFN-? and inflammatory cytokines production in U251 cells.3.miR-22 targets human MAVSWe used a combination of bioinformatics and experimental techniques to demonstrate that mitochondrial antiviral signaling protein(MAVS)is a novel target of miR-22.And miR-22 inhibits endogenous MAVS expression though directly binding to 3'UTR of MAVS mRNA.4.miR-22 negatively regulates poly(I:C)-triggered type I interferon and inflammatory cytokine production via targeting mitochondrial antiviral signaling protein(MAVS)We found that overexpression of MAVS fully rescued the suppression of type I interferon and inflammatory cytokines observed upon miR-22 overexpression.Knockdown of MAVS signifcantly decreased the expression level of IFN-? and inflammatory cytokines,which means that MAVS silencing produces effects similar to those of miR-22 overexpression.Moreover,miR-22 inhibits the activation of IRF3 and NF-?B by targeting MAVS.Together,we demonstrated that miR-22 negatively regulates poly(I:C)-triggered type I interferon and inflammatory cytokine production via targeting MAVS.5.miR-22 facilitates JEV replication in astrocytesmiR-22 was significantly up-regulated in a time and dose-dependent manner during JEV infected U251 cells.Furthermore,we found cells treated with miR-22 enhance JEV replication,whereas miR-22 inhibitors prohibited the proliferation of JEV.In this study,we verified the important role of miR-22 in poly(I:C)-treated cells for the first time.The hypothesis that MAVS is a novel target of miR-22 was verified as well.The study explained the molecular mechanism of miR-22 modulates type I interferon and inflammatory cytokine production,which provides a new way to explore the molecular mechanism of neuroinflammation induced by virus.