Inhibition of Nuclear Factor kB by Phenolic Antioxidants: Interplay Between Antioxidant Signaling and Inflammatory Cytokine Expression

Details

• Personal Author:
  Chen BJ ; Kinneer K ; Ma Q ; Ye J
• 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 tumor necrosis factor (TNF) in macrophages. Hydroquinone and tert-butyl hydroquinone, prototypes of phenolic antioxidants, block lipopolysaccharide (LPS)-induced transcription of TNF and a nuclear factor (NF)-B mediated reporter gene expression, suggesting NF-B as a target in the inhibition. Analyses of the NF-B activation pathway revealed that the antioxidants do not inhibit LPS-induced activation of the IB kinase activity, degradation of IB, or translocation of activated NF-B into the nucleus, but they do block the formation of NF-B/DNA binding complexes. In vitro experiments showed that the antioxidants do not directly interfere with DNA binding of NF-B. Structure-activity analyses suggest that inhibition of NF-B function involves the redox cycling property of the antioxidants. These findings implicate a redox-sensitive factor important for the binding of NF-B to its DNA recognition sequence as a target molecule in the inhibition of NF-B function and inflammatory cytokine expression by phenolic antioxidants. [Description provided by NIOSH]
• Subjects:
  Antioxidants Genetics Neoplasms Occupational Health Safety
• Keywords:
  Genes Genetic-factors In-vitro-study Tumors
• ISSN:
  0026-895X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  211-219
• Volume:
  64
• Issue:
  2
• NIOSHTIC Number:
  nn:20023273
• Citation:
  Mol Pharmacol 2003 Aug; 64(2):211-219
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  True
• Source Full Name:
  Molecular Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:96880e4dec98c95ec4b24b9b179db6c85b7894d9e712ad374932f67f64da97c1b94164af561371d902e4725c01f322257d40b08432c37f3ca14505e6efe007b5
• Download URL:
  https://stacks.cdc.gov/view/cdc/195799/cdc_195799_DS1.pdf
• File Type:
  [PDF - 512.92 KB ]