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Chemoprotection by phenolic antioxidants.

Authors
Ma-Q; Kinneer-K
Source
J Biol Chem 2002 Jan; 25(4):2477-2484
NIOSHTIC No.
20022294
Abstract
Phenolic antioxidants exhibit anti-inflammatory activity in protection against chemical toxicity and cancer. To investigate the molecular mechanism of anti-inflammation, we analyzed the regulation of tumor necrosis factor (TNF-) expression in macrophages, a key step in inflammation, by the antioxidants. Whereas lipopolysaccharide (LPS), an inflammatory inducer, stimulates rapid synthesis of TNF- protein, phenolic antioxidants, exemplified by tert-butyl hydroquinone and 1,4-dihydroquinone, block LPS-induced production of TNF- protein in a time- and dose-dependent manner. Inhibition of TNF- induction correlates with the capacity of the antioxidants to undergo oxidation-reduction cycling, implicating oxidative signaling in the inhibition. The antioxidants blocked LPS-induced increase of the steady-state mRNA of TNF- but did not affect the half-life of the mRNA. Electrophoretic mobility shift assay reveals a total inhibition of LPS-induced formation of nuclear factor BĚDNA binding complexes by phenolic antioxidants. Finally, 1,4-dihydroquinone blocks the induction of TNF- target genes interleukin 1 and interleukin 6 at both mRNA and protein levels. Our findings demonstrate that phenolic antioxidants potently inhibit signal-induced TNF- transcription and suggest a mechanism of anti-inflammation by the antioxidants through control of cytokine induction during inflammation.
Keywords
Phenols; Cancer; Oxidation-reduction-reactions; Antioxidants; Humans
Contact
CDC/NIOSH, Mail Stop 3014, 1095 Willowdale Rd., Morgantown, WV 26505
CODEN
JBCHA3
CAS No.
123-31-9; 108-95-2; 1948-33-0; 7722-84-1
Publication Date
20020125
Document Type
Journal Article
Email Address
qam1@cdc.gov
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
4
ISSN
0021-9258
NIOSH Division
HELD
Source Name
Journal of Biological Chemistry
State
WV
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