Transcription factor-κB (NF-κB) and renal disease

Transcription factor-κB (NF-κB) and renal disease. Nuclear factor-κB (NF-κB) comprises a family of dimeric transcription factors that regulate the expression of numerous genes involved in inflammation and cell proliferation. Although NF-κB was initially identified in lymphocytes, it has been found to be a transcription factor present in virtually all cell types. In resting cells, NF-κB dimers remain in the cytoplasm in an inactive form bound to the inhibitory subunit IκB. Upon stimulation, IκB is phosphorylated, ubiquitinylated, and ultimately degraded by proteolytic cleavage by the proteasome system. As a result, NF-κB dimers are translocated into the nucleus and activate the transcription of target genes. Increasing data suggest a pivotal role for NF-κB in a variety of pathophysiological conditions in which either inflammation or cell number control are critical events. NF-κB has been found to be activated in experimental renal disease. Importantly, both in vivo and in vitro, NF-κB activation can be modulated by pharmacological maneuvers. Indeed, it is now widely acknowledged that the anti-inflammatory action of steroids is basically obtained through the inhibition of the transactivation of NF-κB–dependent genes. In addition, some of the beneficial effects of angiotensin-converting enzyme inhibitors and statins may, at least in part, be mediated by an inhibition of NF-κB activation. A better understanding of the mechanisms involved in NF-κB regulation and its modulation may provide new tools to improve the treatment of renal diseases with a better sound pathophysiological approach.