Histamine may induce airway remodeling through release of epidermal growth factor receptor ligands from bronchial epithelial cells

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 reacti...

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Veröffentlicht in:The FASEB journal 2012-04, Vol.26 (4), p.1704-1716
Hauptverfasser: Hirota, Nobuaki, Risse, Paul‐Andre, Novali, Mauro, McGovern, Toby, Al‐Alwan, Laila, McCuaig, Sarah, Proud, David, Hayden, Patrick, Hamid, Qutayba, Martin, James G.
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container_issue 4
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container_title The FASEB journal
container_volume 26
creator Hirota, Nobuaki
Risse, Paul‐Andre
Novali, Mauro
McGovern, Toby
Al‐Alwan, Laila
McCuaig, Sarah
Proud, David
Hayden, Patrick
Hamid, Qutayba
Martin, James G.
description 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
doi_str_mv 10.1096/fj.11-197061
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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&lt; 0.001; HB‐EGF 2.3‐fold, P&lt;0.05) and triggered their release (amphiregulin EC50 0.50 μM, 31.2±2.7 pg/ml with 10 μM histamine, P&lt;0.01; HB‐EGF EC50 0.54 μM, 78.5±1.8 pg/ml with 10 μM histamine, P&lt;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. 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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&lt; 0.001; HB‐EGF 2.3‐fold, P&lt;0.05) and triggered their release (amphiregulin EC50 0.50 μM, 31.2±2.7 pg/ml with 10 μM histamine, P&lt;0.01; HB‐EGF EC50 0.54 μM, 78.5±1.8 pg/ml with 10 μM histamine, P&lt;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. 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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&lt; 0.001; HB‐EGF 2.3‐fold, P&lt;0.05) and triggered their release (amphiregulin EC50 0.50 μM, 31.2±2.7 pg/ml with 10 μM histamine, P&lt;0.01; HB‐EGF EC50 0.54 μM, 78.5±1.8 pg/ml with 10 μM histamine, P&lt;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. FASEB J. 26, 1704‐1716 (2012). www.fasebj.org</abstract><cop>Bethesda, MD, USA</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>22247333</pmid><doi>10.1096/fj.11-197061</doi><tpages>13</tpages></addata></record>
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subjects Adult
Airway Remodeling - drug effects
Amphiregulin
Asthma - metabolism
Asthma - pathology
Bronchi - cytology
Cell Differentiation - drug effects
Cell Line
Cell Movement
Cell Proliferation
EGF Family of Proteins
Epithelial Cells - cytology
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Glycoproteins - genetics
Glycoproteins - metabolism
goblet cell differentiation
HB‐EGF
Heparin-binding EGF-like Growth Factor
heparin‐binding epidermal growth factor‐like growth factor
Histamine - pharmacology
Humans
Intercellular Signaling Peptides and Proteins - genetics
Intercellular Signaling Peptides and Proteins - metabolism
Ligands
Middle Aged
migration
proliferation
Receptor, Epidermal Growth Factor - metabolism
Receptors, Histamine H1 - metabolism
Young Adult
title Histamine may induce airway remodeling through release of epidermal growth factor receptor ligands from bronchial epithelial cells
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