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Nadia Khorasani,1 Josephine Baker,1 Malcolm Johnson,2 Kian Fan Chung,1 Pankaj K Bhavsar1 1Experimental Studies, Airway Disease Section, National Heart and Lung Institute, Imperial College and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust Hospital, London, UK; 2GlaxoSmithKline, Uxbridge, UK Background: Corticosteroids (CS) have limited efficacy in the treatment of chronic obstructive pulmonary disease (COPD). p38 mitogen-activated protein kinase (MAPK) activation is increased in lung macrophages of COPD. We investigated whether p38 MAPK inhibition can modulate CS insensitivity of peripheral blood mononuclear cells (PBMCs) from patients with COPD. Methods: PBMCs from patients with COPD (n=8) or healthy smokers (n=8) were exposed to lipopolysaccharide (LPS) with a selective p38 MAPK inhibitor (GW856553; 10–10–10–6 M), with dexamethasone (10–10–10–6 M), or with both. Phosphorylated glucocorticoid receptor (GR) was measured by Western blot. Results: Baseline (P |
