We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Histamine may induce airway remodeling through release of epidermal growth factor receptor ligands from bronchial epithelial cells.
- Authors
Hirota, Nobuaki; Risse, Paul-Andre; Novali, Mauro; McGovern, Toby; Al-Alwan, Laila; McCuaig, Sarah; Proud, David; Hayden, Patrick; Hamid, Qutayba; Martin, James G.
- Abstract
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 EC50 0.50 µM, 31.2±2.7 pg/ml with 10 µM histamine, P<0.01; HB-EGF EC50 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.
- Subjects
ASTHMA; CHRONIC diseases; HYPERPLASIA; EPITHELIAL cells; CELL differentiation
- Publication
FASEB Journal, 2012, Vol 26, Issue 4, p1704
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.11-197061