Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-ß Activity.
PLoS Pathog
; 13(1): e1006138, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-28046097
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-ß (TGF-ß) 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-ß. In the current study, we examine the contribution of TGF-ß 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(IC), a synthetic analog of double-stranded RNA, also impairs GC activity. Both viral infection and poly(IC) increase TGF-ß expression and activity. Importantly, the GC impairment was attenuated by the selective ALK5 (TGFßRI) inhibitor, SB431542 and prevented by the therapeutic agent, tranilast, which reduced TGF-ß 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-ß.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
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Fator de Crescimento Transformador beta
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Mucosa Respiratória
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Doença Pulmonar Obstrutiva Crônica
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Glucocorticoides
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Anti-Inflamatórios
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article