title: Evaluation of glucocorticoid receptor function in COPD lung macrophages using beclomethasone-17-monopropionate.
abstract: Previous studies of glucocorticoid receptor (GR) function in COPD lung macrophages have used dexamethasone to evaluate inhibition of cytokine production. We have now used the clinically relevant corticosteroid beclomethasone-17-monopropionate (17-BMP) to assess GR function in COPD lung macrophages, and investigated the transactivation of glucocorticoid sensitive genes and GR phosphorylation in addition to cytokine production. Lung macrophages were purified from surgically acquired lung tissue, from patients with COPD, smokers, and non-smokers. The transactivation of glucocorticoid sensitive genes (FKBP51 and GILZ) by 17-BMP were analysed by polymerase chain reaction. 17-BMP suppression of LPS-induced TNFα, IL-6 and CXCL8 was measured by ELISA and GR phosphorylation was measured by immunohistochemistry and Western blot. 17-BMP reduced cytokine release in a concentration dependent manner, with >70% inhibition of all cytokines, and no difference between COPD patients and controls. Similarly, the transactivation of FKBP51 and GILZ, and GR phosphorylation was similar between COPD patients and controls. In this context, GR function in COPD lung macrophages is unaltered. 17-BMP effectively suppresses cytokine production in COPD lung macrophages.
authors.affiliation: National Institute for Health Research Translational Research Facility, Manchester Academic Health Science Centre, University Hospital of South Manchester Foundation Trust, University of Manchester, Manchester, United Kingdom. jonathan.plumb@manchester.ac.uk
authors.forename: Jonathan
authors.initials: J
authors.lastname: Plumb
authors.forename: Laura
authors.initials: L
authors.lastname: Robinson
authors.forename: Simon
authors.initials: S
authors.lastname: Lea
authors.forename: Antonia
authors.initials: A
authors.lastname: Banyard
authors.forename: John
authors.initials: J
authors.lastname: Blaikley
authors.forename: David
authors.initials: D
authors.lastname: Ray
authors.forename: Andrea
authors.initials: A
authors.lastname: Bizzi
authors.forename: Giorgina
authors.initials: G
authors.lastname: Volpi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Facchinetti
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
mesh_terms: D000368:Aged; D001507:Beclomethasone / Q000031:analogs & derivatives* / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003710:Demography; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D000099159:Tacrolimus Binding Protein 5
chemical_list: D001507:Beclomethasone; D016207:Cytokines; D003907:Dexamethasone; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D014157:Transcription Factors; D000099159:Tacrolimus Binding Protein 5; C404226:TSC22D3 protein, human; C065857:beclomethasone 17-monopropionate