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: Wei Bi, Lihong Zhu, Zhifen Zeng, Xiuna Jing, Yanran Liang, Li Guo, Qiaoyun Shi, Anding Xu, Enxiang Tao
• Journal: Neuroimmunomodulation (Neuroimmunomodulation) Vol. 21 Issue 6 Pg. 331-7 ( 2014) ISSN: 1423-0216 [Electronic] Switzerland
• PMID: 24642793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Lipopolysaccharides
• NF-kappa B
• RNA, Small Interfering
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Proteasome Endopeptidase Complex
• 26S proteasome non-ATPase regulatory subunit 13
• Dinoprostone

Topics

• Animals
• Cell Line, Transformed
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (metabolism)
• Enzyme Inhibitors (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Lipopolysaccharides (pharmacology)
• Mice
• Microglia (drug effects, metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Proteasome Endopeptidase Complex (genetics, metabolism)
• RNA, Small Interfering (pharmacology)
• Transfection