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

The nuclear factor kappa B (NF-κB) 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-κB, but the molecular mechanisms involved in this process remain largely unknown. The signaling pathways mediating cytokine- or microorganism-induced NF-κB activation have been well established recently. Whether the same signaling systems are involved in metal-induced NF-κB activation, however, is unclear. In the present review, we have attempted to evaluate and update the possible mechanisms of signals on the activation and function of NF-κB.