Signaling from toxic metals to NF-kappaB and beyond: not just a matter of reactive oxygen species

Environ Health Perspect. 2002 Oct;110 Suppl 5(Suppl 5):807-11. doi: 10.1289/ehp.02110s5807.


The nuclear factor kappa B (NF-kappaB) family of transcription factors controls expression of a number of early response genes associated with inflammatory responses, cell growth, cell cycle progression, and neoplastic transformation. These genes include a multitude of cytokines, chemokines, adhesion molecules, immune receptors, stress proteins, apoptotic or anti-apoptotic regulators, and several oncogenes. Accumulating evidence indicates that a variety of toxic metals are able to affect the activation or activity of NF-kappaB, but the molecular mechanisms involved in this process remain largely unknown. The signaling pathways mediating cytokine- or microorganism-induced NF-kappaB activation have been well established recently. Whether the same signaling systems are involved in metal-induced NF-kappaB activation, however, is unclear. In the present review, we have attempted to evaluate and update the possible mechanisms of metal signals on the activation and function of NF-kappaB.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Cytokines / pharmacology
  • Gene Expression Regulation
  • Humans
  • Metals, Heavy / adverse effects*
  • Metals, Heavy / pharmacology
  • NF-kappa B / drug effects
  • NF-kappa B / pharmacology*
  • Oxidative Stress*
  • Phosphotransferases / pharmacology
  • Reactive Oxygen Species / adverse effects
  • Signal Transduction


  • Cytokines
  • Metals, Heavy
  • NF-kappa B
  • Reactive Oxygen Species
  • Phosphotransferases