Diesel exhaust increases EGFR and phosphorylated C-terminal Tyr 1173 in the bronchial epithelium
Diesel exhaust increases EGFR and phosphorylated C-terminal Tyr 1173 in the bronchial epithelium
BACKGROUND: epidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is a major contributor to particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, together with an enhanced epithelial expression of cytokines such as IL-8, Gro-alpha, IL-13 and activation of redox sensitive transcription factors (NFkappaB, AP-1), and MAP kinases (p38, JNK). The aim of the present investigation was to elucidate the involvement of the epidermal growth factor receptor (EGFR) signalling pathway in the epithelial response to DE in-vivo.
RESULTS: immunohistochemical staining was used to quantify the expression of the EGFR, phosphorylated Tyrosine residues, MEK and ERK in the bronchial epithelium of archived biopsies from 15 healthy subjects following exposure to DE (PM10, 300 mug/m3) and air. DE induced a significant increases in the expression of EGFR (p = 0.004) and phosphorylated C-terminal Tyr 1173 (p = 0.02). Other investigated EGFR tyrosine residues, Src related tyrosine (Tyr 416), MEK and ERK pathway were not changed significantly by DE.
CONCLUSION: exposure to DE (PM10, 300 mug/m3) caused enhanced EGFR expression and phosphorylation of the tyrosine residue (Tyr 1173) which is in accordance with the previously demonstrated activation of the JNK, AP-1, p38 MAPK and NFkB pathways and associated downstream signalling and cytokine production. No effects were seen on the MEK and ERK pathway suggesting that at the investigated time point (6 hours post exposure) there was no proliferative/differentiation signalling in the bronchial epithelium. The present findings suggest a key role for EGFR in the bronchial response to diesel exhaust.
particulate matter, cytokines, biopsy, epithelium, transcription factors
1-9
Pourazar, Jamshid
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Blomberg, Anders
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Kelly, Frank J.
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Davies, Donna E.
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Wilson, Susan J.
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Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Sandstrom, Thomas
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6 May 2008
Pourazar, Jamshid
d41db41e-cb53-4399-8c77-aaed8ff153a6
Blomberg, Anders
b19c0008-dc79-425d-a05b-2fda60f020cf
Kelly, Frank J.
8eda554f-c23c-4321-b5e2-b99a72dfd0aa
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Sandstrom, Thomas
99593b63-fa97-40b6-a57d-5d7b2b4b1c01
Pourazar, Jamshid, Blomberg, Anders, Kelly, Frank J., Davies, Donna E., Wilson, Susan J., Holgate, Stephen T. and Sandstrom, Thomas
(2008)
Diesel exhaust increases EGFR and phosphorylated C-terminal Tyr 1173 in the bronchial epithelium.
Particle and Fibre Toxicology, 5 (8), .
(doi:10.1186/1743-8977-5-8).
(PMID:18460189)
Abstract
BACKGROUND: epidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is a major contributor to particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, together with an enhanced epithelial expression of cytokines such as IL-8, Gro-alpha, IL-13 and activation of redox sensitive transcription factors (NFkappaB, AP-1), and MAP kinases (p38, JNK). The aim of the present investigation was to elucidate the involvement of the epidermal growth factor receptor (EGFR) signalling pathway in the epithelial response to DE in-vivo.
RESULTS: immunohistochemical staining was used to quantify the expression of the EGFR, phosphorylated Tyrosine residues, MEK and ERK in the bronchial epithelium of archived biopsies from 15 healthy subjects following exposure to DE (PM10, 300 mug/m3) and air. DE induced a significant increases in the expression of EGFR (p = 0.004) and phosphorylated C-terminal Tyr 1173 (p = 0.02). Other investigated EGFR tyrosine residues, Src related tyrosine (Tyr 416), MEK and ERK pathway were not changed significantly by DE.
CONCLUSION: exposure to DE (PM10, 300 mug/m3) caused enhanced EGFR expression and phosphorylation of the tyrosine residue (Tyr 1173) which is in accordance with the previously demonstrated activation of the JNK, AP-1, p38 MAPK and NFkB pathways and associated downstream signalling and cytokine production. No effects were seen on the MEK and ERK pathway suggesting that at the investigated time point (6 hours post exposure) there was no proliferative/differentiation signalling in the bronchial epithelium. The present findings suggest a key role for EGFR in the bronchial response to diesel exhaust.
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1743-8977-5-8
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Published date: 6 May 2008
Keywords:
particulate matter, cytokines, biopsy, epithelium, transcription factors
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Local EPrints ID: 70857
URI: http://eprints.soton.ac.uk/id/eprint/70857
ISSN: 1743-8977
PURE UUID: a807bb1e-a8eb-4ce4-a573-bf41eb479d7f
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Date deposited: 29 Jan 2010
Last modified: 14 Mar 2024 02:32
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Author:
Jamshid Pourazar
Author:
Anders Blomberg
Author:
Frank J. Kelly
Author:
Thomas Sandstrom
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