A gut feeling of the PXR, PPAR and NF-kappaB connection

J Intern Med. 2008 Jun;263(6):613-9. doi: 10.1111/j.1365-2796.2008.01951.x.

Abstract

Bowel diseases reveal the complex interplay of sensing and signalling pathways in maintaining healthy homeostasis of the intestine. Recent studies of the xenobiotic nuclear receptor, pregnane X receptor and the inflammatory mediator nuclear transcription factor kappaB (NF-kappaB) reveal a functional link between xenobiotic neutralization and inflammation and explain how certain xenobiotics can affect the immune response. Furthermore, another nuclear receptor, peroxisome proliferator-activated receptor gamma (PPAR gamma) has been shown to produce beneficial effects in experimental inflammatory bowel diseases by repression of NF-kappaB thereby reducing inflammation, whilst its close relative PPAR beta/delta appears at a central position in signalling pathways involved in the progression of colon cancer. Recently accumulated knowledge on the action of these nuclear receptors and NF-kappaB in intestinal homeostasis may provide the rationale for the development of innovative treatment strategies with selective receptor modulators.

Publication types

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

MeSH terms

  • Cell Transformation, Neoplastic / metabolism
  • Colonic Neoplasms / physiopathology
  • Humans
  • Inflammatory Bowel Diseases / physiopathology*
  • NF-kappa B / physiology*
  • Peroxisome Proliferator-Activated Receptors / physiology*
  • Pregnane X Receptor
  • Receptors, Steroid / physiology*
  • Signal Transduction
  • Xenobiotics / toxicity

Substances

  • NF-kappa B
  • Peroxisome Proliferator-Activated Receptors
  • Pregnane X Receptor
  • Receptors, Steroid
  • Xenobiotics