Epithelial-mesenchymal communication in the pathogenesis of chronic asthma

Holgate, Stephen T., Holloway, John, Wilson, Susan, Bucchieri, Fabio, Puddicombe, Sarah and Davies, Donna E. (2004) Epithelial-mesenchymal communication in the pathogenesis of chronic asthma. Proceedings of the American Thoracic Society, 1 (2), 93-98. (doi:10.1513/pats.2306034).

Abstract

Although Th-2–mediated inflammation is a key therapeutic target in asthma, its relationship to altered structure and functions of the airways is largely unknown. In addition to inflammation, asthma is a disorder involving the airway epithelium that is more vulnerable to environmental injury and responds to this by impaired healing. This establishes a chronic wound scenario that is capable of sustaining chronic inflammation as well as remodeling.
This response occurs as a consequence of activation of the epithelial–mesenchymal unit, involving reciprocal activities of growth factors belonging to the fibroblast growth factor, epidermal growth factor, and transforming growth factor-ß families. The observation that structural changes in the airways in children at or before the onset of asthma occurs irrespective of inflammation might suggest that premodeling is required before Th-2 inflammatory responses can be sustained. Once established, altered function of constitutive airway cells, including fibroblasts, smooth muscle, nerves, and the epithelium, provides an abnormal microenvironment in which to generate a separate set of signals that underpin the acute/subacute inflammation characteristic of asthma exacerbations, triggered by viruses, pollutants, and allergens.

This record has no associated files available for download.

Contributors

Author: John Holloway

Author: Susan Wilson

Author: Donna E. Davies

Download statistics