Haloperidol Abrogates Matrix Metalloproteinase-9 Expression by Inhibition of NF-κ B Activation in Stimulated Human Monocytic Cells

Mediators of Inflammation
Yueh-Lun LeeGeorge Hsiao

Abstract

Much evidence has indicated that matrix metalloproteinases (MMPs) participate in the progression of neuroinflammatory disorders. The present study was undertaken to investigate the inhibitory effect and mechanism of the antipsychotic haloperidol on MMP activation in the stimulated THP-1 monocytic cells. Haloperidol exerted a strong inhibition on tumor necrosis factor- (TNF-) α-induced MMP-9 gelatinolysis of THP-1 cells. A concentration-dependent inhibitory effect of haloperidol was observed in TNF-α-induced protein and mRNA expression of MMP-9. On the other hand, haloperidol slightly affected cell viability and tissue inhibition of metalloproteinase-1 levels. It significantly inhibited the degradation of inhibitor-κB-α (IκBα) in activated cells. Moreover, it suppressed activated nuclear factor-κB (NF-κB) detected by a mobility shift assay, NF-κB reporter gene, and chromatin immunoprecipitation analyses. Consistent with NF-κB inhibition, haloperidol exerted a strong inhibition of lipopolysaccharide- (LPS-) induced MMP-9 gelatinolysis but not of transforming growth factor-β1-induced MMP-2. In in vivo studies, administration of haloperidol significantly attenuated LPS-induced intracerebral MMP-9 activation of the brain homogenate ...Continue Reading

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Methods Mentioned

BETA
Reverse-Transcription Polymerase Chain Reaction
PCR
Assay
electrophoretic mobility shift assay
LightShift
Transfection
Immunoprecipitation
ELISA
transfections
ChIP

Software Mentioned

Pro® Express
Image

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