Faculty Opinions recommendation of Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-β Activity.
Year: 2017
Type: peer-review
Abstract: 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 TGFβ 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.
Author: Johan Neyts
Institution: Rega Institute for Medical Research
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4239794223