Document Detail

The epidermal growth factor receptor mediates allergic airway remodelling in the rat.
MedLine Citation:
PMID:  18653647     Owner:  NLM     Status:  MEDLINE    
The chronicity of bronchial asthma is attributed to persistent airway inflammation and to a variety of structural changes, or remodelling, that includes smooth muscle and goblet cell hyperplasia. To investigate the mechanisms of airway remodelling, the current authors used an established allergen (ovalbumin; OVA)-driven rodent model (the Brown Norway rat). Brown Norway rats were sensitised to OVA and challenged three times at 5-day intervals to evoke airway remodelling. The effects of an epidermal growth factor (EGF) receptor inhibitor, AG1478, and a cysteinyl leukotriene-1 receptor antagonist, montelukast, on epithelial and airway smooth muscle (ASM) cell proliferation in vivo in response to repeated OVA challenge were tested. Three challenges with leukotriene (LT)D(4) were given, to examine their effects on remodelling with and without AG1478 pretreatment. OVA challenges caused ASM hyperplasia, with an increase in mass, epithelial cell proliferation and goblet cell proliferation. AG1478 prevented the changes, as did montelukast. Multiple OVA challenges increased heparin-binding EGF-like growth factor but not EGF expression by airway epithelium. LTD(4) reproduced the changes in remodelling induced by OVA and this was blocked by AG1478. Allergen-induced airway epithelial and airway smooth muscle remodelling is mediated by cysteinyl leukotrienes via the cysteinyl leukotriene-1 receptor with downstream effects on the epidermal growth factor receptor axis.
M Tamaoka; M Hassan; T McGovern; D Ramos-Barbón; T Jo; Y Yoshizawa; B Tolloczko; Q Hamid; J G Martin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-24
Journal Detail:
Title:  The European respiratory journal     Volume:  32     ISSN:  1399-3003     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-03     Completed Date:  2009-05-08     Revised Date:  2013-05-23    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1213-23     Citation Subset:  IM    
Meakins-Christie Laboratories, Dept of Medicine, McGill University, 3626 St Urbain Street, Montreal, QC, H2X 2P2, Canada.
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MeSH Terms
Allergens / metabolism
Cell Proliferation
Cysteine / chemistry
Gene Expression Profiling*
Goblet Cells / pathology*
Hyperplasia / pathology
Leukotriene D4 / metabolism
Muscle, Smooth / metabolism
Ovalbumin / metabolism
Receptor, Epidermal Growth Factor / physiology*
Receptors, Leukotriene / metabolism
Tyrphostins / pharmacology
Reg. No./Substance:
0/Allergens; 0/Quinazolines; 0/Receptors, Leukotriene; 0/Tyrphostins; 170449-18-0/tyrphostin AG 1478; 52-90-4/Cysteine; 73836-78-9/Leukotriene D4; 9006-59-1/Ovalbumin; EC, Epidermal Growth Factor

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