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

Kidney Int. 2001 Feb;59(2):415-24. doi: 10.1046/j.1523-1755.2001.059002415.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Kidney / metabolism
  • Kidney Diseases / etiology*
  • Kidney Diseases / therapy
  • NF-kappa B / chemistry
  • NF-kappa B / physiology*
  • Structure-Activity Relationship

Substances

  • NF-kappa B