Transcription factor-kappa B (NF-kappa B) and renal disease.
Transcription factor-kappa B (NF-kappa B) and renal disease. Nuclear factor-kappa B (NF-kappa B) comprises a family of dimeric transcription factors that regulate the expression of numerous genes involved in inflammation and cell proliferation. Although NF-kappa B was initially identified in lymphocytes, it has been found to be a transcription factor present in virtually all cell types. In resting cells, NF-kappa B dimers remain in the cytoplasm in an inactive form bound to the inhibitory subunit I kappa B. Upon stimulation, I kappa B is phosphorylated, ubiquitinylated, and ultimately degraded by proteolytic cleavage by the proteasome system. As a result, NF-kappa B dimers are translocated into the nucleus and activate the transcription of target genes. Increasing data suggest a pivotal role for NF-kappa B in a variety of pathophysiological conditions in which either inflammation or cell number control are critical events. NF-kappa B has been found to be activated in experimental renal disease. Importantly, both in vivo and in vitro, NF-kappa B 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-kappa B-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-kappa B activation. A better understanding of the mechanisms involved in NF-kappa B regulation and its modulation may provide new tools to improve the treatment of renal diseases with a better sound pathophysiological approach.
Guijarro
C
C
Fundación Hospital Alcorcón, Universidad Autónoma, Madrid, Spain.
Egido
J
J
D000818:Animals; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology* / Q000628:therapy; D016328:NF-kappa B / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship
D016328:NF-kappa B