Ergothioneine inhibits oxidative stress- and TNF-alpha-induced NF-kappa B activation and interleukin-8 release in alveolar epithelial cells

Biochem Biophys Res Commun. 2003 Mar 21;302(4):860-4. doi: 10.1016/s0006-291x(03)00224-9.

Abstract

Oxidants and inflammatory mediators such as tumour necrosis factor-alpha (TNF-alpha) activate transcription factors such as NF-kappa B. Interleukin-8 (IL-8) is a ubiquitous inflammatory chemokine that mediates a multitude of inflammatory events in the lung. Ergothioneine is a naturally occurring thiol compound, which possesses antioxidant property. The aim of this study was to determine whether ergothioneine can inhibit the hydrogen peroxide (H(2)O(2))- and TNF-alpha-mediated activation of NF-kappa B and the release of IL-8 in human alveolar epithelial cells (A549). Treatment of A549 cells with H(2)O(2) (100 microM) and TNF-alpha (10 ng/ml) significantly increased NF-kappa B activation using a reporter assay. Ergothioneine inhibited both H(2)O(2)- and TNF-alpha-mediated activation of NF-kappa B. Both H(2)O(2) and TNF-alpha significantly increased IL-8 release, which was inhibited by pre-treatment of A549 cells with ergothioneine compared to the control untreated cells. Ergothioneine also abolished the transcriptional activation of IL-8 in an IL-8-chloramphenicol acetyltransferase (CAT) reporter system, transfected into A549 cells. This indicates a molecular mechanism for the anti-inflammatory effects of ergothioneine.

MeSH terms

  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Ergothioneine / metabolism
  • Ergothioneine / pharmacology*
  • Genes, Reporter
  • Glutathione / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Interleukin-8 / metabolism*
  • Molecular Structure
  • NF-kappa B / metabolism*
  • Oxidants / metabolism
  • Oxidative Stress*
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / metabolism
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Antioxidants
  • Interleukin-8
  • NF-kappa B
  • Oxidants
  • Tumor Necrosis Factor-alpha
  • Hydrogen Peroxide
  • Ergothioneine
  • Glutathione