In:
Neuroimmunomodulation, S. Karger AG, Vol. 21, No. 6 ( 2014), p. 331-337
Abstract:
〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 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. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 RNA interference was used to knockdown PSMD13 gene expression, followed by inhibitors of & #954;B (I & #954;Ba) protein degradation and nuclear factor & #954;B (NF- & #954;B) activity measurement in lipopolysaccharide (LPS)-stimulated BV2 microglia. Nitrite (Griess) assay, reporter gene assay, enzyme-linked immunosorbent assay and Western blot 〈 b 〉 〈 /b 〉 were used to investigate the role of PSMD13 in microglial activation and inflammation. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 PSMD13 gene knockdown significantly reduced I & #954;Ba degradation and NF- & #954;B 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 E 〈 sub 〉 2 〈 /sub 〉 . 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 PSMD13 gene silencing suppressed the production of proinflammatory mediators by modulating ubiquitin-proteasome system-mediated neuroinflammation via the downregulation of I & #954;Ba degradation and NF- & #954;B activation in LPS-stimulated BV2 microglia. PSMD13 gene knockdown may have therapeutic implications for the treatment of neuroinflammatory disorders.
Type of Medium:
Online Resource
ISSN:
1021-7401
,
1423-0216
Language:
English
Publisher:
S. Karger AG
Publication Date:
2014
detail.hit.zdb_id:
1184368-8
detail.hit.zdb_id:
1483035-8
