Abstract
In this report we explored the effects of proteasome inhibitors (MG132, aLLN, lactacystin and MG262) on interleukin-8 (IL-8) induction. In HEK293 cells, proteasome inhibitors could concentration-dependently increase IL-8 promoter and activator protein-1 (AP-1) activities, but inhibited nuclear factor (NF)-kappa B activation induced by cytokines. The stimulating effects on IL-8 promoter and AP-1 were reduced by N-acetylcysteine, glutathione, diphenyleneiodonium, rotenone and antimycin A. Fluorescent analysis using 2',7'-dichlorodihydrofluorescin diacetate further confirmed the abilities of proteasome inhibitors to induce reactive oxygen species (ROS) production. These results suggest that ROS production by proteasome inhibitors leads to AP-1 activation, which in the absence of NF-kappa B activation still transactivates IL-8 gene expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcysteine / analogs & derivatives*
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Acetylcysteine / metabolism
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Acetylcysteine / pharmacology*
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Antioxidants / pharmacology*
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Cell Line
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Cysteine Endopeptidases / metabolism*
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Cysteine Proteinase Inhibitors / pharmacology*
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Gene Expression Regulation / drug effects
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Genes, Reporter
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Humans
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Interleukin-8 / genetics
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Leupeptins / pharmacology*
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Luciferases / genetics
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Multienzyme Complexes / metabolism*
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Promoter Regions, Genetic / drug effects
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Proteasome Endopeptidase Complex
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Reactive Oxygen Species / metabolism*
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Recombinant Proteins / metabolism
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Transcription Factor AP-1 / metabolism*
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Transfection
Substances
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Antioxidants
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Cysteine Proteinase Inhibitors
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Interleukin-8
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Leupeptins
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Multienzyme Complexes
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Reactive Oxygen Species
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Recombinant Proteins
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Transcription Factor AP-1
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lactacystin
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Luciferases
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde
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Acetylcysteine