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

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