PPAR-γ activity is deficient in alveolar macrophages of allergic asthmatics

Abstract

Rationale Recent studies have suggested that peroxisome proliferator-activated receptor-γ (PPAR-γ), a ligand-activated nuclear transcription factor, may be a negative modulator of inflammation and macrophage gene expression. We hypothesized that because of the chronic inflammation in asthmatic airways, PPAR-γ expression may be decreased in allergic asthmatics. Methods Bronchoalveolar lavage (BAL) cells from mild asthmatic patients (n=4) and healthy controls (n=5) were evaluated for PPAR-γ expression by quantitative real time PCR (ABI) and immunocytochemistry at baseline and 24h post segmental allergen (grass or ragweed) challenge. Results Baseline BAL cell differentials were not different between asthmatics (mean 96% alveolar macrophages) and healthy controls (94%). Asthmatics had allergen-induced late asthmatic reactions as shown by increased eosinophils with allergen challenge (mean 28% ± 11) versus healthy control (2 ± 1). Relative PPAR-γ gene expression normalized to GAPDH expression was decreased significantly in asthmatics at baseline (25 ± 6) relative to healthy controls (90 ± 36) and further decreased with challenge (6 ± 3), p=0.03. In contrast no significant change was observed in healthy controls post challenge (62 ± 15). Immunostaining with anti-PPAR-γ demonstrated decreased nuclear PPAR-γ expression in alveolar macrophages from asthmatics. Conclusions These studies are the first to suggest PPAR-γ may not be appropriately up-regulated in alveolar macrophages from allergic asthmatics and deficient PPAR-γ may contribute to chronic inflammation.