Inhaled long-acting β2 agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD

• Published in: Journal of allergy and clinical immunology 2013-11, Vol.132 (5), p.1166-1173
• Main Authors: Haque, Rubaiyat, MBBS, Hakim, Amir, PhD, Moodley, Thunicia, PhD, Torrego, Alfonso, MD, Essilfie-Quaye, Sarah, PhD, Jazrawi, Elen, BSc, Johnson, Malcolm, PhD, Barnes, Peter J., FRS, FMedSci, Adcock, Ian M., PhD, FSB, Usmani, Omar Sharif, MBBS, PhD
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adrenal Cortex Hormones - administration & dosage; Adrenal Cortex Hormones - therapeutic use; Adrenergic beta-2 Receptor Agonists - administration & dosage; Adrenergic beta-2 Receptor Agonists - therapeutic use; Aged; Allergy and Immunology; Biological and medical sciences; Cell Line; Cell Nucleus - metabolism; Chromosome aberrations; COPD; corticosteroid; Dual Specificity Phosphatase 1 - genetics; Dual Specificity Phosphatase 1 - metabolism; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Genes, Reporter; glucocorticoid receptor; Humans; Immunopathology; Interleukin-1beta - pharmacology; Interleukin-8 - genetics; Interleukin-8 - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Long-acting β2 agonist; macrophage; Macrophages - drug effects; Macrophages - metabolism; Male; Medical genetics; Medical sciences; Middle Aged; Protein Binding; Protein Transport - drug effects; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; Receptors, Glucocorticoid - metabolism; Response Elements; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; sputum; Sputum - cytology; U937 Cells
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2013.07.038

Background Combination inhaled therapy with long-acting β2  agonists (LABAs) and corticosteroids is beneficial in treating asthma and chronic obstructive pulmonary disease (COPD). Objective In asthma, LABAs enhance glucocorticoid receptor (GR) nuclear translocation in the presence of corticosteroids. Whether this biological mechanism occurs in COPD, a relatively corticosteroid-resistant disease, is uncertain. Methods Eight patients with mild/moderate COPD participated in a double-blind, placebo-controlled, crossover study and inhaled single doses of fluticasone propionate (FP) 100 μg, FP 500 μg, salmeterol xinafoate (SLM) 50 μg, and combination FP 100 μg + SLM 50 μg. One hour postinhalation, sputum was induced, nuclear proteins isolated from purified macrophages, and levels of activated nuclear GR quantified by using a GR-glucocorticoid response element ELISA-based assay. Results Nuclear GR significantly increased after the inhalation of FP 500 μg ( P