Barrier responses of human bronchial epithelial cells to grass pollen exposure
Barrier responses of human bronchial epithelial cells to grass pollen exposure
The airway epithelium forms a physical, chemical and immunological barrier against inhaled environmental substances. In asthma, these barrier properties are thought to be abnormal. Here, we analysed the effect of grass pollen on the physical and immunological barrier properties of differentiated human primary bronchial epithelial cells.Following exposure to Timothy grass (Phleum pratense) pollen extract, the integrity of the physical barrier was not impaired as monitored by measuring the transepithelial resistance and immunofluorescence staining of tight junction proteins. In contrast, pollen exposure affected the immunological barrier properties by modulating vectorial mediator release. CXCL8/IL-8 showed the greatest increase in response to pollen exposure with preferential release to the apical compartment. Inhibition of the ERK1/2 and p38 MAPK pathways selectively blocked apical CXCL8/IL-8 release via a post transcriptional mechanism. Apical release of CCL20/MIP-3?, CCL22/MDC and TNF? was significantly increased only in severe asthma cultures, while CCL11/eotaxin-1 and CXCL10/IP-10 were reduced in non-asthmatic cultures.The bronchial epithelial barrier modulates polarised release of mediators in response to pollen without direct effects on its physical barrier properties. The differential response of cells from normal and asthmatic donors suggests the potential for the bronchial epithelium to promote immune dysfunction in asthma.
asthma, epithelial barrier, mitogen-activated protein kinase signalling pathway, polarised mediator release, protein trafficking, tight junctions
Blume, Cornelia
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Swindle, Emily J.
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Dennison, Patrick
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Jayasekera, Nivenka P.
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Dudley, Sarah
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Monk, Phillip
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Behrendt, Heidrun
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Schmidt-Weber, Carsten B.
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Holgate, Stephen T.
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Howarth, Peter H.
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Traidl-Hoffmann, Claudia
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Davies, Donna E.
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Blume, Cornelia
aa391c64-8718-4238-906b-d6bb1551a07b
Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f
Dennison, Patrick
45948aae-8297-4459-be11-56e85f51ae73
Jayasekera, Nivenka P.
18db967c-b59a-430f-b0e8-e89cb8ba8efe
Dudley, Sarah
a7b1dfb4-4e02-4b96-8232-c9304136ae08
Monk, Phillip
f0b35062-133d-4d96-8347-742d27a46fa6
Behrendt, Heidrun
384c18c5-3895-4053-8755-ec760ff449dc
Schmidt-Weber, Carsten B.
1bbdced2-957f-4b8f-a45c-fa0ebb25a044
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Traidl-Hoffmann, Claudia
65194201-2f2b-4521-8b2c-ed02ca59ef0b
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Blume, Cornelia, Swindle, Emily J., Dennison, Patrick, Jayasekera, Nivenka P., Dudley, Sarah, Monk, Phillip, Behrendt, Heidrun, Schmidt-Weber, Carsten B., Holgate, Stephen T., Howarth, Peter H., Traidl-Hoffmann, Claudia and Davies, Donna E.
(2012)
Barrier responses of human bronchial epithelial cells to grass pollen exposure.
European Respiratory Journal.
(doi:10.1183/09031936.00075612).
(PMID:23143548)
Abstract
The airway epithelium forms a physical, chemical and immunological barrier against inhaled environmental substances. In asthma, these barrier properties are thought to be abnormal. Here, we analysed the effect of grass pollen on the physical and immunological barrier properties of differentiated human primary bronchial epithelial cells.Following exposure to Timothy grass (Phleum pratense) pollen extract, the integrity of the physical barrier was not impaired as monitored by measuring the transepithelial resistance and immunofluorescence staining of tight junction proteins. In contrast, pollen exposure affected the immunological barrier properties by modulating vectorial mediator release. CXCL8/IL-8 showed the greatest increase in response to pollen exposure with preferential release to the apical compartment. Inhibition of the ERK1/2 and p38 MAPK pathways selectively blocked apical CXCL8/IL-8 release via a post transcriptional mechanism. Apical release of CCL20/MIP-3?, CCL22/MDC and TNF? was significantly increased only in severe asthma cultures, while CCL11/eotaxin-1 and CXCL10/IP-10 were reduced in non-asthmatic cultures.The bronchial epithelial barrier modulates polarised release of mediators in response to pollen without direct effects on its physical barrier properties. The differential response of cells from normal and asthmatic donors suggests the potential for the bronchial epithelium to promote immune dysfunction in asthma.
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e-pub ahead of print date: 8 November 2012
Keywords:
asthma, epithelial barrier, mitogen-activated protein kinase signalling pathway, polarised mediator release, protein trafficking, tight junctions
Organisations:
Clinical & Experimental Sciences
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Local EPrints ID: 346644
URI: http://eprints.soton.ac.uk/id/eprint/346644
ISSN: 0903-1936
PURE UUID: 36eab98e-2145-4575-8f7a-c52fcd66eebf
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Date deposited: 16 Jan 2013 10:11
Last modified: 15 Mar 2024 03:35
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Author:
Patrick Dennison
Author:
Nivenka P. Jayasekera
Author:
Sarah Dudley
Author:
Phillip Monk
Author:
Heidrun Behrendt
Author:
Carsten B. Schmidt-Weber
Author:
Claudia Traidl-Hoffmann
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