Epithelial-mesenchymal communication in the pathogenesis of chronic asthma.
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-beta 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.
Holgate
Stephen T
ST
Respiratory Cell and Molecular Biology, Infection, Inflammation and Repair Division, School of Medicine, University of Southampton, D Level Centre Block, Southampton General Hospital, Southampton SO16 6YD, UK. s.holgate@soton.ac.uk
Holloway
John
J
Wilson
Susan
S
Bucchieri
Fabio
F
Puddicombe
Sarah
S
Davies
Donna E
DE
D001249:Asthma / Q000276:immunology* / Q000503:physiopathology*; D002908:Chronic Disease; D016207:Cytokines / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D018448:Models, Immunological; D009130:Muscle, Smooth / Q000503:physiopathology; D012143:Respiratory Physiological Phenomena; D018418:Th2 Cells / Q000276:immunology; D014945:Wound Healing
D016207:Cytokines; D006133:Growth Substances