Reversal of corticosteroid insensitivity by p38 MAPK inhibition in peripheral blood mononuclear cells from COPD

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...

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Bibliographic Details
Published in:International journal of chronic obstructive pulmonary disease 2015-01, Vol.10 (Issue 1), p.283-291
Main Authors: Khorasani, Nadia, Baker, Josephine, Johnson, Malcolm, Chung, Kian Fan, Bhavsar, Pankaj K
Format: Article
Language:English
Subjects:
Adrenal Cortex Hormones - pharmacology
Aged
Antibodies
Care and treatment
Case-Control Studies
Cells, Cultured
Chronic obstructive pulmonary disease
Corticosteroids
Cyclopropanes - pharmacology
Cytokines
Dexamethasone - pharmacology
Dose-Response Relationship, Drug
Drug Resistance
Enzymes
Female
Gene expression
Genetic aspects
Health aspects
Humans
Interleukin-6 - metabolism
Interleukin-8 - metabolism
Kinases
Leukocytes, Mononuclear - drug effects
Leukocytes, Mononuclear - enzymology
Leukocytes, Mononuclear - immunology
Lipopolysaccharides - pharmacology
Lung diseases, Obstructive
Male
Middle Aged
Original Research
p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases - metabolism
Patient outcomes
Phosphorylation
Protein Kinase Inhibitors - pharmacology
Protein kinases
Proteins
Pulmonary Disease, Chronic Obstructive - blood
Pulmonary Disease, Chronic Obstructive - drug therapy
Pulmonary Disease, Chronic Obstructive - enzymology
Pulmonary Disease, Chronic Obstructive - immunology
Pyridines - pharmacology
Receptors, Glucocorticoid - agonists
Receptors, Glucocorticoid - metabolism
Serine
Smoking
Steroids
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Summary: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. 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. Baseline (P
ISSN:1178-2005
1176-9106
1178-2005
DOI:10.2147/COPD.S72403