Dysregulated or constitutive NF-κB activity, however, has been functionally linked to the development of a wide range of disorders such as carcinoma and I/R injury; activated NF-κB, induced by pro-inflammatory cytokines (e.g. IL-1 and TNF-α) and endogenous ligands for Toll-like receptors (TLRs) that are generated in response to ischemia and the high level of ROS produced during reperfusion, enhancing even more pro-inflammatory cytokines and pro-apoptotic proteins that may cause tissue or organ injury. Here, TNF is linked to ischemia.