title: Investigations into the role of 26S proteasome non-ATPase regulatory subunit 13 in neuroinflammation.
abstract: OBJECTIVE
  To investigate 26S proteasome non-ATPase regulatory subunit 13 (PSMD13) gene silencing as a potential treatment for neuroinflammatory disorders via regulation of microglial activation and production of inflammatory mediators.
  
  
  METHODS
  RNA interference was used to knockdown PSMD13 gene expression, followed by inhibitors of κB (IκBα) protein degradation and nuclear factor κB (NF-κB) activity measurement in lipopolysaccharide (LPS)-stimulated BV2 microglia. Nitrite (Griess) assay, reporter gene assay, enzyme-linked immunosorbent assay and Western blot were used to investigate the role of PSMD13 in microglial activation and inflammation.
  
  
  RESULTS
  PSMD13 gene knockdown significantly reduced IκBα degradation and NF-κB activation in LPS-stimulated murine BV2 microglia. It also decreased the production of LPS-induced proinflammatory mediators, such as inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and prostaglandin E2.
  
  
  CONCLUSIONS
  PSMD13 gene silencing suppressed the production of proinflammatory mediators by modulating ubiquitin-proteasome system-mediated neuroinflammation via the downregulation of IκBα degradation and NF-κB activation in LPS-stimulated BV2 microglia. PSMD13 gene knockdown may have therapeutic implications for the treatment of neuroinflammatory disorders.
authors.affiliation: Department of Neurology, First Affiliated Hospital of Jinan University, Guangzhou, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bi
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhu
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Zeng
authors.forename: Xiuna
authors.initials: X
authors.lastname: Jing
authors.forename: Yanran
authors.initials: Y
authors.lastname: Liang
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Shi
authors.forename: Anding
authors.initials: A
authors.lastname: Xu
authors.forename: Enxiang
authors.initials: E
authors.lastname: Tao
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D046988:Proteasome Endopeptidase Complex; C119011:26S proteasome non-ATPase regulatory subunit 13; D015232:Dinoprostone