TY - JOUR T1 - Diminished peroxisome proliferator-activated receptor (PPAR) regulation as a potential mechanism for the persistent inflammation in chronic obstructive pulmonary disease JF - European Respiratory Review JO - EUROPEAN RESPIRATORY REVIEW SP - 211 LP - 212 DO - 10.1183/09059180.00010124 VL - 15 IS - 101 AU - E. M. Drost AU - C. A. Poland AU - K. Donaldson AU - W. MacNee Y1 - 2006/12/01 UR - http://err.ersjournals.com/content/15/101/211.abstract N2 - Persistent inflammation is the main pathological process that underlies COPD. Understanding this inflammatory response is a key focus of COPD research with the aim of discovering new therapeutic targets. The nuclear hormone receptor, PPAR is now a recognised modulator of inflammation in various chronic inflammatory conditions, but its role in the persistent airways inflammation in COPD has not been examined. Control of the inflammatory response by PPARα has been shown by antagonising inflammatory signalling pathways, such as NF-κB and AP-1. PPARα protein levels in lung tissue from patients with COPD were assessed by Western blot. In vitro assays using the human type II alveolar epithelial cell line were performed to assess the effect of PPARα agonist treatment on inflammatory cytokine generation. An increase in PPARα protein levels was seen for healthy smokers compared with non-smokers (Ratio to β-actin loading control, non-smokers 0.61±0.1, n = 10; healthy smokers 0.97±0.3, n = 11, p>0.05). No increase was seen for current smoker or ex-smoker COPD patients (0.36±0.08, n = 12; 0.49±0.1, n = 8 respectively). In vitro experiments with a human type II alveolar epithelial cell line demonstrated a diminished inflammatory response to TNFα, as measured by the generation of the pro-inflammatory cytokine IL-8, following pre-treatment with the PPARα agonist, WY-14643 (IL-8 generation, control 823±22 pg·ml−1, TNFα 7491±530 pg·ml−1 p<0.001, WY-14643 2559±46 pg·ml−1 p<0.05, n = 3). We propose PPAR agonists as a potential therapy for reducing the NF-κB-regulated inflammation in COPD airways. Supported by GlaxoSmithKline ER -