Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARβ/δ ligand GW0742
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- Haskova, Z., Hoang, B., Luo, G. et al. Inflamm. res. (2008) 57: 314. doi:10.1007/s00011-007-7157-4
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.
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.
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.
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.