TY  - JOUR
AU  - Xia, YC
AU  - Radwan, A
AU  - Keenan, CR
AU  - Langenbach, SY
AU  - Li, M
AU  - Radojicic, D
AU  - Londrigan, SL
AU  - Gualano, RC
AU  - Stewart, AG
Y2  - 2020/12/22
Y1  - 2017/01/01
SN  - 1553-7366
UR  - http://hdl.handle.net/11343/257975
AB  - 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.
LA  - English
PB  - PUBLIC LIBRARY SCIENCE
T1  - Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-beta Activity
DO  - 10.1371/journal.ppat.1006138
IS  - PLoS Pathogens
VL  - 13
IS  - 1
OP  - 1059665
OP  - 1072108
L1  - /bitstream/handle/11343/257975/PMC5234851.pdf?sequence=1&isAllowed=y
ER  -