Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPAR[beta]/[delta] ligand GW0742

• Published in: Inflammation research 2008-07, Vol.57 (7), p.314
• Main Authors: Haskova, Z, Hoang, B, Luo, G, Morgan, L A, Billin, A N, Barone, F C, Shearer, B G, Barton, M E, Kilgore, K S
• Format: Article
• Language: English
• ISSN: 1023-3830; 1420-908X
• 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. [PUBLICATION ABSTRACT]