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 (IκBa) 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 IκBa 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 IκBa degradation and NF-κB activation in LPS-stimulated BV2 microglia. PSMD13 gene knockdown may have therapeutic implications for the treatment of neuroinflammatory disorders.