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Inhibition of TNFalpha promoter/enhancer activity by phenolic antioxidants.
Kinneer KL; Ye J; Ma Q
Toxicologist 2002 Mar; 66(1-S):355
Exposure to occupational chemicals often elicits inflammatory responses, resulting in tissue damage and disease. The cytokine Tumor necrosis factor alpha (TNFalpha) is an important mediator in the early stages of inflammation and plays an essential role in many inflammatory diseases. Certain phenolic antioxidants exhibit anti-inflammatory activity and thereby protect against chemical toxicity. The mechanism of anti-inflammation by the antioxidants is largely unclear. In a previously study, we demonstrated that phenolic antioxidants block signal-induced TNF alpha protein and mRNA production in macrophage cells. In this study, we further investigate the molecular mechanism of this inhibition by analyzing the effect of the antioxidants on the promoter/enhancer activity of TNF alpha. We used a stable reporter cell line that expresses luciferase under the control of TNF alpha promoter/enhancer for measuring TNF alpha gene transcription. The data reveal that bacterial endotoxin LPS induces luciferase production and tert-butylhydroquinone (tBHQ), a prototype of phenolic antioxidants, blocks this induction in the cell. The inhibition is both time- and dose-dependent. Inhibition of LPS-induced transcription of TNF alpha by diphenols (hydroquinone, HQ; catechol, and resorcinol) correlates with their capacity to undergo redox cycling. Furthermore, tBHQ and HQ blocked LPS-induced H2O2 generation within the cell, while resorcinol did not. Treatment with N-acetyl-cysteine, a general ROS inhibitor, blocks LPS-induced luciferase expression similarly. Taken together, these findings demonstrate phenolic antioxidants inhibit TNF alpha gene transcription and implicate redox cycling in the inhibition.
Occupational-exposure; Tissue-disorders; Tumors; Phenolic-compounds; Genes; Cellular-reactions; Endotoxins
The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee
Page last reviewed: March 3, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division