Inflammation Research

, Volume 57, Issue 7, pp 314–321

Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARβ/δ ligand GW0742

  • Z. Haskova
  • B. Hoang
  • G. Luo
  • L. A. Morgan
  • A. N. Billin
  • F. C. Barone
  • B. G. Shearer
  • M. E. Barton
  • K. S. Kilgore
Article

DOI: 10.1007/s00011-007-7157-4

Cite this article as:
Haskova, Z., Hoang, B., Luo, G. et al. Inflamm. res. (2008) 57: 314. doi:10.1007/s00011-007-7157-4

Abstract.

Objective:

To define the anti-inflammatory effects of PPARβ/δ activation by use of the selective PPARβ/δ ligand (GW0742) in a model of lipopolysaccharide (LPS)-induced pulmonary inflammation.

Methods:

Male BALB/c mice were pretreated for three days with the PPARβ/δ agonist, GW0742, prior to induction of LPS-mediated pulmonary inflammation. Bronchial alveolar lavage fluid (BALF) was analyzed for inflammatory cell influx and for levels of pro-inflammatory mediators. BALF-derived inflammatory cells were also collected for mRNA analysis.

Results:

Pretreatment with GW0742 resulted in a significant decrease in leukocyte recruitment into the pulmonary space. Protein and mRNA levels of the pro-inflammatory cytokines IL-6, IL-1β and TNFα in BALF were found to be significantly decreased in GW0742-treated animals (30 mg/kg). A significant decrease in granulocyte macrophage-colony stimulating factor (GM-CSF), a major regulator of neutrophil chemotaxis (via its downstream actions on TNFα and other cytokines/chemokines), activation and survival, was also noted in the BALF levels of GW0742-treated animals.

Conclusions:

The present study demonstrates that activation of PPARβ/δ attenuates the degree of inflammation in a model of LPS-induced pulmonary inflammation and may therefore represent a novel therapeutic approach for the treatment of inflammation-mediated pathologies.

Keywords:

PPARβ/δ agonismPPARβ/δ activatorsInflammationLipopolysaccharide-induced inflammationPulmonary injuryNeutrophiliaCytokines

Copyright information

© Birkhaueser 2008

Authors and Affiliations

  • Z. Haskova
    • 1
  • B. Hoang
    • 2
  • G. Luo
    • 3
  • L. A. Morgan
    • 2
  • A. N. Billin
    • 3
  • F. C. Barone
  • B. G. Shearer
    • 3
  • M. E. Barton
    • 4
  • K. S. Kilgore
    • 5
  1. 1.Biopharmaceutical Center for Excellence in Drug DiscoveryGlaxoSmithKlineKing of PrussiaUSA
  2. 2.Molecular Discovery ResearchGlaxoSmithKline PharmaceuticalsKing of PrussiaUSA
  3. 3.Molecular Discovery ResearchGlaxoSmithKline PharmaceuticalsResearch Triangle ParkUSA
  4. 4.Clinical Pharmacology and Discovery MedicineGlaxoSmithKlineCollegevilleUSA
  5. 5.ImmunoInflammation Center for Excellence in Drug DiscoveryGlaxoSmithKlineCollegevilleUSA