The effects of dexamethasone on cigarette smoke induced gene expression changes in COPD macrophages

• Published in: International immunopharmacology Vol. 10; no. 1; pp. 57 - 64
• Main Authors: Kent, Lauren M., Fox, Steve M., Farrow, Stuart N., Singh, Dave
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 2010; Elsevier
• Subjects: Aged; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cells, Cultured; Chronic obstructive pulmonary disease, asthma; COPD; Cytokine; Cytokines - genetics; Cytokines - metabolism; Dexamethasone; Dexamethasone - pharmacology; Gene Expression Profiling; Gene Expression Regulation - drug effects; Humans; Immunity, Innate - drug effects; Inflammation Mediators - metabolism; Interleukin-8 - genetics; Interleukin-8 - metabolism; Macrophage; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Male; Medical sciences; Microarray; Middle Aged; Oligonucleotide Array Sequence Analysis; Pharmacology. Drug treatments; Pneumology; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - etiology; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; Smoking - adverse effects; Tobacco, tobacco smoking; Toxicology; Dexamethasone; Microarray; Cytokine; COPD; Macrophage; Corticosteroid; Lung disease; Steroid hormone; Respiratory disease; Antiinflammatory agent; Tobacco smoking; Gene expression; Cigarette; Bronchus disease; Obstructive pulmonary disease
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2009.09.021

Chronic obstructive pulmonary disease (COPD) is a smoking related inflammatory airway disease in which macrophages play a key role. Previously we have shown that cigarette smoke extract (CSE) causes suppression of macrophage inflammatory mediators, with the exception of IL-8. We now investigate the effects of dexamethasone on these gene expression changes. Monocyte derived macrophages (MDMs) were cultured with CSE and dexamethasone. Microarray analysis was used to assess inflammatory mediator regulation, with qPCR and ELISA also performed for selected cytokines. The major effect of CSE was down-regulation of inflammatory genes (11 probe sets). For CSE regulated genes ( n = 13), the median fold change with CSE alone was − 2.84 and with dexamethasone alone was − 2.97. Both treatments combined caused the greatest suppression of gene expression; − 4.47. qPCR also showed that IL-1β, GM-CSF and IL-6 mRNA levels were significantly reduced by CSE and further suppressed by dexamethasone. qPCR and ELISA showed that IL-8 levels were increased by CSE, with suppression by dexamethasone. We show that CSE suppressed the expression of some inflammatory genes whilst up-regulating IL-8. Dexamethasone further suppressed gene expression when combined with CSE. The combined effect of GC and CSE causes suppression of the macrophage innate immune response.