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Inhibition of nuclear factor kB by phenolic antioxidants: interplay between antioxidant signaling and inflammatory cytokine expression.

Authors
Ma-Q; Kinneer-K; Ye-J; Chen-BJ
Source
Mol Pharmacol 2003 Aug; 64(2):211-219
NIOSHTIC No.
20023273
Abstract
Phenolic antioxidants inhibit the induction of inflammatory cytokines by inflammatory stimuli. Here, we analyzed the mechanism by which the antioxidants inhibit LPS-induced expression of tumor necrosis factor (TNF) in macrophages. Hydroquinone and tert-butyl hydroquinone, prototypes of phenolic antioxidants, block lipopolysaccharide (LPS)-induced transcription of TNF and a nuclear factor (NF)-B mediated reporter gene expression, suggesting NF-B as a target in the inhibition. Analyses of the NF-B activation pathway revealed that the antioxidants do not inhibit LPS-induced activation of the IB kinase activity, degradation of IB, or translocation of activated NF-B into the nucleus, but they do block the formation of NF-B/DNA binding complexes. In vitro experiments showed that the antioxidants do not directly interfere with DNA binding of NF-B. Structure-activity analyses suggest that inhibition of NF-B function involves the redox cycling property of the antioxidants. These findings implicate a redox-sensitive factor important for the binding of NF-B to its DNA recognition sequence as a target molecule in the inhibition of NF-B function and inflammatory cytokine expression by phenolic antioxidants.
Keywords
Antioxidants; Tumors; Genetic-factors; Genes; In-vitro-study
CODEN
MOPMA3
Publication Date
20030801
Document Type
Journal Article
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0026-895X
NIOSH Division
HELD
Source Name
Molecular Pharmacology
State
WV; LA
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