NF-κB is normally sequestered in the cytoplasm by its inhibitor, IκB. Upon stimulation by toxic agents such as reactive oxygen species (ROS), heavy metals, or certain drugs, IκB is phosphorylated and degraded, releasing NF-κB to translocate to the nucleus. This activation can be triggered by receptor-mediated pathways, such as those involving tumor necrosis factor (TNF) receptors or Toll-like receptors, which are commonly implicated in the cellular response to environmental toxins.
