MicroRNA367 negatively regulates the inflammatory response of microglia by targeting IRAK4 in intracerebral hemorrhage

Background: intracerebral hemorrhage (ich) induces microglial activation and the release of inflammatory cytokines,leading to inflammation in the brain. irak4,an essential component of the myd88-dependent pathway,activates subsets of divergent signaling pathways in inflammation. methods: in the experiment,microglia were stimulated with erythrocyte lysates,and then mir-367,irak4,nf-κb activation and downstream proinflammatory mediator production were analyzed. in addition,inflammation,brain edema,and neurological functions in ich mice were also assessed. results: here,we report that ich downregulated mir-367 expression but upregulated irak4 expression in primary microglia. we also demonstrate that mir-367 suppressed irak4 expression by directly binding its 3'-untranslated region. mir-367 inhibited nf-κb activation and downstream proinflammatory mediator production. knocking down irak4 in microglia significantly decreased the irak4 expression and inhibited the nf-κb activation and the downstream production of proinflammatory mediators. in addition,our results indicate that mir-367 could inhibit expression of proinflammatory cytokines,reduce brain edema,and improve neurological functions in ich mice. conclusions: in conclusion,our study demonstrates that mir-367/irak4 pathway plays an important role in microglial activation and neuroinflammation in ich. our finding also suggests that mir-367 might represent a potential therapeutic target for ich. © 2015 yuan et al.