Chemoprotection by Phenolic Antioxidants
Public Domain
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2002/01/25
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Description: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 B·DNA 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. [Description provided by NIOSH]
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ISSN:0021-9258
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Volume:277
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Issue:4
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NIOSHTIC Number:nn:20022294
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Citation:J Biol Chem 2002 Jan; 25(4):2477-2484
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Contact Point Address:CDC/NIOSH, Mail Stop 3014, 1095 Willowdale Rd., Morgantown, WV 26505
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Email:qam1@cdc.gov
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CAS Registry Number:
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Federal Fiscal Year:2002
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Peer Reviewed:True
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Source Full Name:Journal of Biological Chemistry
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Main Document Checksum:urn:sha-512:950d6aaacf6ec018eafae0a94bae3e2ba079994471ec9301632e59cbcae5dc777c7c6e5f1ab74cb97514a634ce916d8f129dc7b57f79fa786c1a4ef21a17b516
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