Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-β Activity

Asthma and chronic obstructive pulmonary disease (copd) exacerbations are commonly associated with respiratory syncytial virus (rsv),rhinovirus (rv) and influenza a virus (iav) infection. the ensuing airway inflammation is resistant to the anti-inflammatory actions of glucocorticoids (gcs). viral infection elicits transforming growth factor-β (tgf-β) activity,a growth factor we have previously shown to impair gc action in human airway epithelial cells through the activation of activin-like kinase 5 (alk5),the type 1 receptor of tgf-β. in the current study,we examine the contribution of tgf-β activity to the gc-resistance caused by viral infection. we demonstrate that viral infection of human bronchial epithelial cells with rsv,rv or iav impairs gc anti-inflammatory action. poly(i:c),a synthetic analog of double-stranded rna,also impairs gc activity. both viral infection and poly(i:c) increase tgf-β expression and activity. importantly,the gc impairment was attenuated by the selective alk5 (tgfβri) inhibitor,sb431542 and prevented by the therapeutic agent,tranilast,which reduced tgf-β activity associated with viral infection. this study shows for the first time that viral-induced glucocorticoid-insensitivity is partially mediated by activation of endogenous tgf-β. © 2017 xia et al.