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Inhibition of lipopolysaccharide-induced gene expression by liver X receptor ligands in macrophages involves

Paloma Guillem-Llobat1, Miguel A Íñiguez1

  • 1Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Nicolás Cabrera, 1, Cantoblanco, 28049 Madrid, Spain.

Prostaglandins, Leukotrienes, and Essential Fatty Acids
|March 5, 2015
PubMed

Insights

Liver X receptors (LXRs) and retinoid X receptors (RXRs) activation reduces inflammatory gene expression in macrophages. This activation inhibits key inflammatory mediators like COX-2 and mPGES-1, offering potential anti-inflammatory strategies.

Area of Science:

  • Molecular Biology
  • Immunology
  • Pharmacology

Background:

  • Liver X receptors (LXRs) are nuclear receptors that regulate gene expression.
  • LXRs form heterodimers with retinoid X receptors (RXRs).
  • Pro-inflammatory genes like COX-2 and mPGES-1 are crucial in inflammatory responses.

Purpose of the Study:

  • To investigate the effect of LXR/RXR activation on the expression of pro-inflammatory genes in activated macrophages.
  • To determine if LXR/RXR activation can reduce the production of inflammatory mediators.

Main Methods:

  • Treatment of activated macrophages with LXR and RXR ligands.
  • Assessment of COX-2 and mPGES-1 gene expression.
  • Measurement of prostaglandin E2 (PGE2) production.
  • Analysis of transcription factor activity, including NFκB and Egr-1.

Main Results:

  • LXR/RXR activation significantly decreased LPS-induced expression of COX-2 and mPGES-1.
  • Prostaglandin E2 production was substantially reduced following LXR/RXR ligand treatment.
  • LXR/RXR activation interfered with the transcriptional activation of these genes.
  • Interference with NFκB and notably Egr-1 transcription factor activity was observed.

Conclusions:

  • LXR/RXR activation exhibits anti-inflammatory effects in macrophages.
  • The mechanism involves the repression of pro-inflammatory genes like COX-2 and mPGES-1.
  • Interference with Egr-1 signaling by LXR/RXR activation represents a novel anti-inflammatory pathway.
Keywords:
COX-2Egr-1LXRMacrophagesRXRmPGES-1

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