Invited Lecture: Activation of the Epithelial Mesenchymal Trophic Unit in the Pathogenesis of AsthmaHolgate S.T. · Lackie P.M. · Howarth P.H. · Roche W.R. · Puddicombe S.M. · Richter A. · Wilson S.J. · Holloway J.W. · Davies D.E.
Respiratory Cell and Molecular Biology Division, School of Medicine, Southampton General Hospital, Southampton, UK
Background: A recent NIH Workshop and an ERS Task Force concluded that more work was needed to understand mechanisms of severe and chronic asthma. This report describes a series of studies that identify aberrant epithelial mesenchymal signalling in the airways as an important event in maintaining inflammation and driving remodelling in response to environmental injury. Methods: Immunohistochemistry, genotyping and functional studies conducted on cultured asthmatic cells and mucosal biopsies were used to identify biochemical pathways involved in epithelial injury and repair in asthma and their relationship to disease severity. Results: Our findings suggest that the asthmatic state results from an interaction between a susceptible epithelium and Th-2-mediated inflammation to alter the communication between the epithelium and the underlying mesenchyme – the epithelial mesenchymal trophic unit – leading to disease persistence, airway remodelling and refractoriness to corticosteroid treatment. Conclusions: Asthma is more than an inflammatory disorder, but requires engagement of important signalling pathways involved in epithelial repair and tissue remodelling. These pathways involving EGFRs and TGF-βRs provide targets against which to develop novel therapies for chronic asthma.
© 2001 S. Karger AG, Basel
Correspondence to: Dr. Stephen T. Holgate
Respiratory Cell and Molecular Biology Division, School of Medicine
Southampton General Hospital
Southampton SO16 6YD (UK)
This study was supported by Ono Pharmaceutical Company, Osaka, Japan.
Number of Print Pages : 6
Number of Figures : 0, Number of Tables : 0, Number of References : 35
International Archives of Allergy and Immunology
Vol. 124, No. 1-3, Year 2001 (Cover Date: January-March 2001)
Journal Editor: D. Kraft, Vienna
ISSN: 1018–2438 (print), 1423–0097 (Online)
For additional information:http://www.karger.com/journals/iaa