title: MicroRNA367 negatively regulates the inflammatory response of microglia by targeting IRAK4 in intracerebral hemorrhage.
abstract: 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-ĸB 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-ĸB activation and downstream proinflammatory mediator production. Knocking down IRAK4 in microglia significantly decreased the IRAK4 expression and inhibited the NF-ĸB 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.
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian, 350025, China. bangqingyuan@hotmail.com.
authors.forename: Bangqing
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian, 350025, China. hanchaoshen@hotmail.com.
authors.forename: Hanchao
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian, 350025, China. lilin@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian, 350025, China. tonggangsu@hotmail.com.
authors.forename: Tonggang
authors.initials: T
authors.lastname: Su
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China. mimigirls@sina.com.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China. yangzhao5140@sohu.com.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism; D001923:Brain Chemistry; D001929:Brain Edema / Q000473:pathology; D004912:Erythrocytes / Q000187:drug effects; D055785:Gene Knockdown Techniques; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D007276:Injections, Intraventricular; D035683:MicroRNAs / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects*; D016328:NF-kappa B / Q000187:drug effects; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018836:Inflammation Mediators; C000605976:MIRN367 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; C000605977:IRAK4 protein, rat; D017346:Protein Serine-Threonine Kinases