Inhibition of Nuclear Factor Kappa B by Phenolic Antioxidants: Interplay Between Antioxidant Signaling and Inflammatory Cytokine Expression
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2004/03/01
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Description: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 TN approximately in macrophages. Hydroquinone (HQ) and t-butyl hydroquinone (tBHQ), prototypes of phenolic antioxidants, block LPS-induced transcription of TN approximately and a NF-kB-mediated reporter gene expression, suggesting NF-kB as a target in the inhibition. Analyses of the NF- kB activation pathway revealed that the antioxidants do not inhibit LPS-induced activation of the IkB kinase activity, degradation of IkB approximately or translocation of activated NF-kB into the nucleus, but block the formation of NF-k B/DNA binding complexes. In vitro experiments showed that the antioxidants do not directly interfere with DNA binding of NF-kB. Structure-activity analyses suggest that inhibition of NF-kB function involves the redox cycling property of the antioxidants. These findings implicate a redox-sensitive factor important for the binding of NF-kB to its DNA recognition sequence as a target molecule in the inhibition of NF-kB function and inflammatory cytokine expression by phenolic antioxidants. [Description provided by NIOSH]
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ISSN:1096-6080
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Volume:78
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NIOSHTIC Number:nn:20025158
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Citation:Toxicologist 2004 Mar; 78(S-1):324
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Federal Fiscal Year:2004
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Peer Reviewed:False
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Source Full Name:The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland
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Supplement:S-1
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Main Document Checksum:urn:sha-512:f5e939511293b85799f1ca06e1157ad4c042f0da9b50f749553fba99cf3943d4dcfb9881956193ef15051ed38fac1e60af466f6a2965727d4bf9b964d62ca211
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