Inhibition of nuclear factor kappa B by phenolic antioxidants: interplay between antioxidant signaling and inflammatory cytokine expression.
Toxicologist 2004 Mar; 78(S-1):324
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.
Phenols; Antioxidants; Genes; In-vitro-studies; Cell-damage; Cellular-reactions; Cellular-structures; Subcellular-structure
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland