Dexamethasone rescues TGF-β1-mediated β₂-adrenergic receptor dysfunction and attenuates phosphodiesterase 4D expression in human airway smooth muscle cells.

ABSTRACT: Glucocorticoids (GCs) and β₂-adrenergic receptor (β₂AR) agonists improve asthma outcomes in most patients. GCs also modulate gene expression in human airway smooth muscle (HASM), thereby attenuating airway inflammation and airway hyperresponsiveness that define asthma. Our previous studies showed that the pro-fibrotic cytokine, transforming growth factor- β1 (TGF-β1) increases phosphodiesterase 4D (PDE4D) expression that attenuates agonist-induced levels of intracellular cAMP. Decreased cAMP levels then diminishes β₂ agonist-induced airway relaxation. In the current study, we investigated whether glucocorticoids reverse TGF-β1-effects on β₂-agonist-induced bronchodilation and modulate pde4d gene expression in HASM. Dexamethasone (DEX) reversed TG

SUBMITTER: Chung E 

PROVIDER: S-EPMC7545943 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature