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dc.contributor.authorXia, YC
dc.contributor.authorRadwan, A
dc.contributor.authorKeenan, CR
dc.contributor.authorLangenbach, SY
dc.contributor.authorLi, M
dc.contributor.authorRadojicic, D
dc.contributor.authorLondrigan, SL
dc.contributor.authorGualano, RC
dc.contributor.authorStewart, AG
dc.date.accessioned2020-12-22T03:59:55Z
dc.date.available2020-12-22T03:59:55Z
dc.date.issued2017-01-01
dc.identifierpii: PPATHOGENS-D-16-01363
dc.identifier.citationXia, Y. C., Radwan, A., Keenan, C. R., Langenbach, S. Y., Li, M., Radojicic, D., Londrigan, S. L., Gualano, R. C. & Stewart, A. G. (2017). Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-beta Activity. PLOS PATHOGENS, 13 (1), https://doi.org/10.1371/journal.ppat.1006138.
dc.identifier.issn1553-7366
dc.identifier.urihttp://hdl.handle.net/11343/257975
dc.description.abstractAsthma 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.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleGlucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-beta Activity
dc.typeJournal Article
dc.identifier.doi10.1371/journal.ppat.1006138
melbourne.affiliation.departmentPharmacology and Therapeutics
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.source.titlePLoS Pathogens
melbourne.source.volume13
melbourne.source.issue1
melbourne.identifier.nhmrc1059665
melbourne.identifier.nhmrc1072108
dc.rights.licenseCC BY
melbourne.elementsid1183155
melbourne.contributor.authorRadojicic, Danica
melbourne.contributor.authorXia, Yuxiu
melbourne.contributor.authorLangenbach, Shenna
melbourne.contributor.authorLondrigan, Sarah
melbourne.contributor.authorGualano, Rosa
melbourne.contributor.authorStewart, Alastair
melbourne.contributor.authorKeenan, Christine
melbourne.contributor.authorLi, Meina
dc.identifier.eissn1553-7374
melbourne.identifier.fundernameidNHMRC, 1059665
melbourne.identifier.fundernameidNHMRC, 1072108
melbourne.accessrightsOpen Access


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