Pregnane X receptor as a target for treatment of inflammatory bowel disorders

Trends Pharmacol Sci. 2012 Jun;33(6):323-30. doi: 10.1016/j.tips.2012.03.003. Epub 2012 May 18.

Abstract

Pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, has a major role in the induction of genes involved in drug transport and metabolism. Recent studies in mice have provided insight into a novel function for PXR in inflammatory bowel disease (IBD). The mechanism of the protective effect of PXR activation on IBD is not fully established, but is due in part to the attenuation of nuclear factor (NF)-κB signaling that results in lower expression of proinflammatory cytokines. Recent clinical trials with the antibiotic rifaximin, a PXR agonist in the gastrointestinal system, have revealed its potential therapeutic value in the treatment of intestinal inflammation in humans. Thus, PXR may be a novel target for IBD therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / metabolism
  • Mice
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Pregnane X Receptor
  • Receptors, Steroid / agonists*
  • Rifamycins / therapeutic use*
  • Rifaximin
  • Signal Transduction / physiology

Substances

  • Cytokines
  • Gastrointestinal Agents
  • NF-kappa B
  • NR1I2 protein, human
  • Nr1i2 protein, mouse
  • Pregnane X Receptor
  • Receptors, Steroid
  • Rifamycins
  • Rifaximin