A liver-X-receptor ligand, T0901317, attenuates IgE production and airway remodeling in chronic asthma model of mice

PLoS One. 2014 Mar 28;9(3):e92668. doi: 10.1371/journal.pone.0092668. eCollection 2014.

Abstract

The liver-X-receptors have shown anti-inflammatory ability in several animal models of respiratory disease. Our purpose is to investigate the effect of LXR ligand in allergen-induced airway remodeling in mice. Ovalbumin-sensitized mice were chronically challenged with aerosolized ovalbumin for 8 weeks. Some mice were administered a LXR agonist, T0901317 (12.5, 25, 50 mg/kg bodyweight) before challenge. Then mice were evaluated for airway inflammation, airway hyperresponsiveness and airway remodeling. T0901317 failed to attenuate the inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid. But the application of T0901317 reduced the thickness of airway smooth muscle and the collagen deposition. Meanwhile, T0901317 treatment evidently abolished the high level of OVA-specific IgE, TGF-β1 and MMP-9 in lung. So LXRs may attenuate the progressing of airway remodeling, providing a potential treatment of asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Remodeling / drug effects*
  • Allergens / pharmacology
  • Animals
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Bronchoalveolar Lavage Fluid
  • Collagen / metabolism
  • Female
  • Hydrocarbons, Fluorinated / pharmacology*
  • Immunoglobulin E / metabolism*
  • Inflammation / metabolism
  • Ligands
  • Liver X Receptors
  • Lung / drug effects
  • Lung / metabolism
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Inbred BALB C
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism
  • Orphan Nuclear Receptors / metabolism*
  • Ovalbumin / pharmacology
  • Sulfonamides / pharmacology*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Allergens
  • Hydrocarbons, Fluorinated
  • Ligands
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Sulfonamides
  • T0901317
  • Transforming Growth Factor beta1
  • Immunoglobulin E
  • Ovalbumin
  • Collagen
  • Matrix Metalloproteinase 9

Grants and funding

Funded by the National Natural Science Foundation of China grant 81100010. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.