IngentaConnect Epithelial damage and response

Abstract:

Epithelial damage is a characteristic feature of asthma. The epithelium is not merely a passive barrier but can generate a range of mediators that may play a role in the inflammatory and remodelling responses that occur in the lungs in asthma. For example, the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF), whose principal source is the epithelium, can prolong eosinophil survival while transforming growth factor is a potent profibrogenic cytokine. Deposition of collagen in the epithelial subbasement membrane is a characteristic feature of the remodelling response in asthma. This may be due to abnormal associations between myofibroblasts and epithelium, both of which are involved in early lung development (epithelial-mesenchymal trophic unit). In asthma, there may be a primary defect in the epithelium such that it responds abnormally to various stimuli and cannot undergo the normal repair response. Epidermal growth factor (EGF) appears to be a key factor in bronchial epithelial repair; it stimulates epithelial cell proliferation and migration. The 3v isoform of the adhesion molecule CD44 is overexpressed in damaged epithelium and seems to regulate the repair response by presenting EGF more efficiently to its receptor. Although EGF receptor expression is increased in asthma, it does not lead to an appropriate proliferative response and restitution of normal epithelium. Other factors such as transforming growth factor (TGF)β which are generated by inflammatory cells and epithelium are also upregulated in asthma. An epithelial/fibroblast co-culture system has shown that following epithelial damage various growth factors are released from the underlying myofibroblasts and are responsible for the proliferative response. The TGFβ family are most likely responsible for collagen production. In an in vitro study, an EGF receptor inhibitor slowed epithelial repair but enhanced TGFβ production by the slowly repairing epithelial cells. In conclusion, the interaction between epithelial cells and myofibroblasts, i.e. reactivation of the epithelial-mesenchymal trophic unit appears to be central to the airway wall remodelling response.

Keywords: asthma; epithelium; epidermal growth factor; myofibroblasts; repair; proliferation; transforming growth factor

Document Type: Research article

DOI: 10.1046/j.1365-2222.2000.00095.x

Affiliations: 1: Southampton General Hospital, UK

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