Addressing corticosteroid insensitivity in adults with asthma

Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma.

BACKGROUND About 5-10% of patients with asthma suffer from poorly controlled disease despite corticosteroid (CS) treatment, which may indicate the presence of CS insensitivity. A study was undertaken to determine whether relative CS insensitivity is present in alveolar macrophages from patients with severe asthma and its association with p38 mitogen-activated protein kinase (MAPK) activation an...

Protein phosphatase 5 mediates corticosteroid insensitivity in airway smooth muscle in patients with severe asthma.

BACKGROUND The mechanisms driving glucocorticoid (GC) insensitivity in patients with severe asthma are still unknown. Recent evidence suggests the existence of GC-insensitive pathways in airway smooth muscle (ASM) caused by a defect in GC receptor (GRα) function. We examined whether other mechanisms could potentially explain the reduced sensitivity of ASM cells to GC in severe asthmatics. MET...

Corticosteroid insensitivity in severe asthma: impaired nuclear translocation of glucocorticoid receptor in airway smooth muscle cells

Methods ASMC of the healthy (12), non-severe (NSA; 10) and severe asthma (SA; 10) obtained from endobronchial biopsies were pretreated with dexamethasone (Dex) at 10-10 M followed by stimulation with TNF-a and IFN-g (10 ng/ml each), alone or in combination (T+I). CXCL8 and CCL11 release was determined by ELISA, GR and p65 protein was assessed by Western Blot, mRNA by RT-qPCR and p65 recruitment...

Defects of Protein Phosphatase 2A Causes Corticosteroid Insensitivity in Severe Asthma

BACKGROUND Corticosteroid insensitivity is a major barrier of treatment for some chronic inflammatory diseases, such as severe asthma, but the molecular mechanism of the insensitivity has not been fully elucidated. The object of this study is to investigate the role of protein phosphate 2A (PP2A), a serine/threonine phosphatase, on corticosteroid sensitivity in severe asthma. METHODOLOGY/PRIN...

Inhaled corticosteroid dosage in asthma.