Journal article

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

Yuxiu C Xia, Asmaa Radwan, Christine R Keenan, Shenna Y Langenbach, Meina Li, Danica Radojicic, Sarah L Londrigan, Rosa C Gualano, Alastair G Stewart

PLoS Pathogens | PUBLIC LIBRARY SCIENCE | Published : 2017

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 h..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by University of Melbourne (UoM)


Awarded by NHMRC


Funding Acknowledgements

This work was supported by: National Health and Medical Research Council (NHMRC) research grant (www.nhmrc.gov.au) APP1059665 to AGS, The University of Melbourne Early Career Researcher Grant (UoM ECR) (research.unimelb.edu.au) APP602017 to YCX, and the NHMRC Peter Doherty-Australian Biomedical Fellowship APP1072108 to YCX. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.