The epidermal growth factor receptor and its ligand family: their potential role in repair and remodelling in asthma.
The bronchial epithelium acts as a physical barrier to the ingress of airborne irritants and plays an active role in the airways immune response, reacting to a range of environmental stimuli to enable interaction with immune and inflammatory cells. It is well established that mucosal damage and epithelial cell shedding are important features of inflammatory airways diseases such as asthma. Evidence now suggests that the repairing epithelium has the potential to contribute to disease chronicity through production of an array of soluble mediators and adhesion molecules. However, the biochemical mechanisms that control epithelial maintenance and repair are poorly understood, even though avoiding or reversing the changes in the airways which are likely to result from chronic inflammation and epithelial restitution remains a significant challenge in asthma therapy. The purpose of this review is to highlight the potential of the epidermal growth factor receptor (EGFR/c-erbB) and its ligands in restitution of the bronchial epithelium. This receptor tyrosine kinase plays a pivotal role in regulation of epithelial cell behaviour, having the capacity to elicit a broad spectrum of cellular responses ranging from migration or proliferation to differentiation and enhanced survival; it also has the ability to regulate expression of various inflammatory mediators, mucins, adhesion molecules, matrix proteins, and metalloproteinases which are relevant to the chronic disease phenotype.
Davies
D E
DE
University Medicine, Southampton General Hospital, UK.
Polosa
R
R
Puddicombe
S M
SM
Richter
A
A
Holgate
S T
ST
D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001980:Bronchi / Q000378:metabolism / Q000473:pathology*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009092:Mucous Membrane / Q000378:metabolism
D066246:ErbB Receptors