Transcription factor-kappa B (NF-kappa B) and renal disease

Nuclear factor-kappaB (NF-kappaB) comprises a family of dimeric transcripti on factors that regulate the expression of numerous genes involved in infla mmation 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. Up on 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 transcrip tion 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 v itro. NF-kappaB activation can be modulated by pharmacological maneuvers. I ndeed. it is now widely acknowledged that the antiinflammatory action of st eroids is basically obtained through the inhibition of the transactivation of NF-kappaB-dependent genes. In addition, some of the beneficial effects o f angiotensin-converting enzyme inhibitors and statins may, at least in par t, be mediated by an inhibition of NF-kappaB activation. A better understan ding of the mechanisms involved in NF-kappaB regulation and its modulation may provide new tools to improve the treatment of renal diseases with a bet ter sound pathophysiological approach.