title: MicroRNA-223 acts as an important regulator to Kupffer cells activation at the early stage of Con A-induced acute liver failure via AIM2 signaling pathway.
abstract: BACKGROUND
  Acute liver failure (ALF), known as a rapid and severe clinical syndrome, can induce multiple organ dysfunction and failure. It was noticed that Kupffer cells activation at the initial phase was involved in some intense inflammatory responses in the pathogenesis of ALF. However, detailed regulation mechanism of Kupffer cells activation during ALF is still obscured. Present study aimed to discover the potential regulator and explore deeper information of Kupffer cells activation at the early stage of ALF.
  
  
  METHODS
  The mouse model of ALF was established by Concanavalin A injection. Dynamic immunological statuses of Kupffer cells at the early stage of ALF were exhibited by detecting typical cytokines. The expression of inflammasome AIM2 was measured in both RNA and protein level. Its role of affecting Kupffer cells activation during ALF by inducing IL-1β production was identified by RNA interference in vitro. Moreover, the expression of miR-223 in vivo was measured by q-PCR and its role in regulating Kupffer cells activation during Con A induced ALF was determined by RNAs transfection.
  
  
  RESULTS
  Present study showed that mass production of IL-1β from isolated Kupffer cells in Con A treated mice might be the main driving force of Kupffer cells pro-inflammatory activation during ALF. The role of AIM2 in affecting pro-inflammatory activation of Kupffer cells by inducing IL-1β production was crucial to ALF. Further study found that miR-223 acted as a regulator in Kupffer cells activation at the early stage of ALF by influencing IL-1β production via AIM2 pathway.
  
  
  CONCLUSIONS
  For the first time, this paper demonstrated that miR-223 acted to inhibit IL-1β production via AIM2 pathway, suppressing Kupffer cells pro-inflammatory activation at the early stage of ALF. Thus, it played an important role in the pathogenesis of ALF.
authors.affiliation: State Key Laboratory of Infectious Diseases Diagnosis and Treatment, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Guohua
authors.initials: G
authors.lastname: Lou
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Jiliang
authors.initials: J
authors.lastname: He
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D007728:Kupffer Cells / Q000473:pathology*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction
chemical_list: C540422:Aim2 protein, mouse; D004268:DNA-Binding Proteins; D053583:Interleukin-1beta; C544877:MIRN223 microRNA, mouse; D035683:MicroRNAs