Urban particulate matter induces pro-remodeling factors by airway epithelial cells from healthy and asthmatic children

Abstract

Context: Chronic exposure to ambient particulate matter pollution during childhood is associated with decreased lung function growth and increased prevalence of reported respiratory symptoms. The role of airway epithelium-derived factors has not been well determined.

Objective: To determine if urban particulate matter (UPM) stimulates production of vascular endothelial growth factor (VEGF) and transforming growth factor-β₂ (TGF-β₂), and gene expression of mucin 5AC (MUC5AC) and interleukin-(IL)-8 by primary airway epithelial cells (AECs) obtained from carefully phenotyped healthy and atopic asthmatic school-aged children.

Methods: Primary AECs from 9 healthy and 14 asthmatic children were differentiated in air--liquid interface (ALI) culture. The apical surface was exposed to UPM suspension or phosphate buffered saline (PBS) vehicle control for 96 h. VEGF and TGF-β₂ concentrations in cell media at baseline, 48 and 96 h were measured via ELISA. MUC5AC and IL-8 expression by AECs at 96 h was measured via quantitative polymerase chain reaction.

Results: Baseline concentrations of VEGF, but not TGF-β₂, were significantly higher in asthmatic versus healthy cultures. UPM stimulated production of VEGF, but not TGF-β₂, at 48 and 96 h; the magnitude of change was comparable across groups. At 96 h there was greater MUC5AC and IL-8 expression by UPM exposed compared to PBS exposed AECs.

Conclusions: Induction of the pro-remodeling cytokine VEGF may be a potential mechanism by which UPM influences lung function growth in children irrespective of asthma status. Respiratory morbidity associated with UPM exposure in children may be related to increased expression of MUC5AC and IL-8.

• Adolescent
• airway remodeling
• asthma
• child
• epithelial cells
• interleukin-8
• mucin 5AC
• particulate matter
• transforming growth factor-β₂
• vascular endothelial growth factor

Acknowledgements

The authors are grateful to the children and parents who participated in this study and to Dr Stephen R. Reeves for his helpful comments on an earlier draft of this manuscript.