Document Detail

Histamine may induce airway remodeling through release of epidermal growth factor receptor ligands from bronchial epithelial cells.
MedLine Citation:
PMID:  22247333     Owner:  NLM     Status:  Publisher    
Asthma is a chronic inflammatory disease that is associated with airway remodeling, including hyperplasia of airway epithelial cells and airway smooth muscle cells, and goblet cell differentiation. We wished to address the potential role of histamine, a key biogenic amine involved in allergic reactions, in airway remodeling through the epidermal growth factor receptor (EGFR) pathway. Here, we demonstrate that histamine releases 2 EGFR ligands, amphiregulin and heparin-binding epidermal growth factor-like growth factor (HB-EGF), from airway epithelial cells. Amphiregulin and HB-EGF were expressed in airway epithelium of patients with asthma. Histamine up-regulated their mRNA expression (amphiregulin 3.2-fold, P<0.001; HB-EGF 2.3-fold, P<0.05) and triggered their release (amphiregulin EC(50) 0.50 μM, 31.2±2.7 pg/ml with 10 μM histamine, P<0.01; HB-EGF EC(50) 0.54 μM, 78.5±1.8 pg/ml with 10 μM histamine, P<0.001) compared to vehicle control (amphiregulin 19.3±0.9 pg/ml; HB-EGF 60.2±1.0 pg/ml), in airway epithelial cells. Histamine increased EGFR phosphorylation (2.1-fold by Western blot analysis) and induced goblet cell differentiation (CLCA1 up-regulation by real-time qPCR) in normal human bronchial epithelial (NHBE) cells. Moreover, amphiregulin and HB-EGF caused proliferation and migration of both NHBE cells and human airway smooth muscle cells. These results suggest that histamine may induce airway remodeling via the epithelial-derived EGFR ligands amphiregulin and HB-EGF.-Hirota, N., Risse, P.-A., Novali, M., McGovern, T., Al-Alwan, L., McCuaig, S., Proud, D., Hayden, P., Hamid, Q., Martin, J. G. Histamine may induce airway remodeling through release of epidermal growth factor receptor ligands from bronchial epithelial cells.
Nobuaki Hirota; Paul-Andre Risse; Mauro Novali; Toby McGovern; Laila Al-Alwan; Sarah McCuaig; David Proud; Patrick Hayden; Qutayba Hamid; James G Martin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-12
Journal Detail:
Title:  The FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  -     ISSN:  1530-6860     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
*Meakins-Christie Laboratories, Department of Medicine, McGill University, Montréal, Québec, Canada;
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