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Epithelial-mesenchymal interactions in the pathogenesis of asthma

Epithelial-mesenchymal interactions in the pathogenesis of asthma
Epithelial-mesenchymal interactions in the pathogenesis of asthma
During lung development, repair, and inflammation, local production of cytokines (eg, transforming growth factor-beta) and growth factors (eg, epidermal growth factor) by epithelial and mesenchymal cells mediate bidirectional growth control effectively creating an epithelial-mesenchymal trophic unit. In asthma the bronchial epithelium is highly abnormal, with structural changes involving separation of columnar cells from their basal attachments and functional changes including increased expression and release of proinflammatory cytokines, growth factors, and mediator-generating enzymes. Beneath this damaged structure there is an increase in the number of subepithelial myofibroblasts that deposit interstitial collagens causing thickening and increased density of the subepithelial basement membrane. Our recent studies suggest that the extent of epithelial damage in asthma may be the result of impaired epidermal growth factor receptor-mediated repair. In view of the close spatial relationship between the damaged epithelium and the underlying myofibroblasts, we propose that impaired epithelial repair cooperates with the T(H)2 environment to shift the set point for communication within the trophic unit. This leads to myofibroblast activation, excessive matrix deposition, and production of mediators that propagate and amplify the remodeling responses throughout the airway wall.
0091-6749
193-204
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Lackie, Peter M.
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Puddicombe, Sarah M.
fd8d76d1-203d-4f06-a7c2-678c946fb931
Lordan, James L.
15a9bdfb-bf61-4aea-a0f4-d83868eb39d0
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Lackie, Peter M.
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Puddicombe, Sarah M.
fd8d76d1-203d-4f06-a7c2-678c946fb931
Lordan, James L.
15a9bdfb-bf61-4aea-a0f4-d83868eb39d0

Holgate, Stephen T., Davies, Donna E., Lackie, Peter M., Wilson, Susan J., Puddicombe, Sarah M. and Lordan, James L. (2000) Epithelial-mesenchymal interactions in the pathogenesis of asthma. Journal of Allergy and Clinical Immunology, 105 (2), part 1, 193-204. (doi:10.1016/S0091-6749(00)90066-6). (PMID:10669837)

Record type: Article

Abstract

During lung development, repair, and inflammation, local production of cytokines (eg, transforming growth factor-beta) and growth factors (eg, epidermal growth factor) by epithelial and mesenchymal cells mediate bidirectional growth control effectively creating an epithelial-mesenchymal trophic unit. In asthma the bronchial epithelium is highly abnormal, with structural changes involving separation of columnar cells from their basal attachments and functional changes including increased expression and release of proinflammatory cytokines, growth factors, and mediator-generating enzymes. Beneath this damaged structure there is an increase in the number of subepithelial myofibroblasts that deposit interstitial collagens causing thickening and increased density of the subepithelial basement membrane. Our recent studies suggest that the extent of epithelial damage in asthma may be the result of impaired epidermal growth factor receptor-mediated repair. In view of the close spatial relationship between the damaged epithelium and the underlying myofibroblasts, we propose that impaired epithelial repair cooperates with the T(H)2 environment to shift the set point for communication within the trophic unit. This leads to myofibroblast activation, excessive matrix deposition, and production of mediators that propagate and amplify the remodeling responses throughout the airway wall.

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Published date: February 2000

Identifiers

Local EPrints ID: 190943
URI: https://eprints.soton.ac.uk/id/eprint/190943
ISSN: 0091-6749
PURE UUID: 965e78c0-f651-4cf1-a52d-03f25254e1c3
ORCID for Peter M. Lackie: ORCID iD orcid.org/0000-0001-7138-3764

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Date deposited: 17 Jun 2011 08:13
Last modified: 30 Jun 2018 00:35

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