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

Jie Cheng1, Yatrik M Shah, Frank J Gonzalez

  • 1Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Trends in Pharmacological Sciences
|May 22, 2012
PubMed

Insights

Pregnane X receptor (PXR) activation shows protective effects against inflammatory bowel disease (IBD) by reducing inflammation. PXR may be a promising therapeutic target for treating IBD in humans.

Area of Science:

  • Molecular Biology
  • Immunology
  • Pharmacology

Background:

  • Pregnane X receptor (PXR) is a nuclear receptor involved in drug metabolism and transport.
  • Emerging research indicates a role for PXR in inflammatory bowel disease (IBD) pathogenesis.
  • The precise mechanisms underlying PXR's influence on IBD are under investigation.

Purpose of the Study:

  • To elucidate the novel function of PXR in inflammatory bowel disease (IBD) based on recent mouse studies.
  • To investigate the protective mechanisms of PXR activation in IBD.
  • To evaluate PXR as a potential therapeutic target for intestinal inflammation.

Main Methods:

  • Review of recent studies in mice investigating PXR's role in IBD.
  • Analysis of PXR's impact on nuclear factor (NF)-κB signaling pathways.
  • Consideration of clinical trial data for PXR agonists like rifaximin in human intestinal inflammation.

Main Results:

  • PXR activation demonstrates a protective effect in experimental models of IBD.
  • PXR activation attenuates nuclear factor (NF)-κB signaling.
  • This attenuation leads to reduced expression of proinflammatory cytokines.

Conclusions:

  • PXR plays a significant role in modulating intestinal inflammation.
  • PXR activation offers a potential therapeutic strategy for IBD.
  • Rifaximin, a PXR agonist, shows promise in treating human intestinal inflammation, supporting PXR as a therapeutic target.

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