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IL-1alpha mediates cellular cross-talk in the airway epithelial mesenchymal trophic unit

IL-1alpha mediates cellular cross-talk in the airway epithelial mesenchymal trophic unit
IL-1alpha mediates cellular cross-talk in the airway epithelial mesenchymal trophic unit
The bronchial epithelium and underlying fibroblasts form an epithelial mesenchymal trophic unit (EMTU) which controls the airway microenvironment. We hypothesised that cell-cell communication within the EMTU propagates and amplifies the innate immune response to respiratory viral infections.

EMTU co-culture models incorporating polarized (16HBE14o-) or differentiated primary human bronchial epithelial cells (HBECs) and fibroblasts were challenged with double-stranded RNA (dsRNA) or rhinovirus.

In the polarized EMTU model, dsRNA affected ionic but not macromolecular permeability or cell viability. Compared with epithelial monocultures, dsRNA-stimulated pro-inflammatory mediator release was synergistically enhanced in the basolateral compartment of the EMTU model, with the exception of IL-1alpha which was unaffected by the presence of fibroblasts. Blockade of IL-1 signalling with IL-1 receptor antagonist (IL-1Ra) completely abrogated dsRNA-induced basolateral release of mediators except CXCL10. Fibroblasts were the main responders to epithelial-derived IL-1 since exogenous IL-1alpha induced pro-inflammatory mediator release from fibroblast but not epithelial monocultures. Our findings were confirmed in a differentiated EMTU model where rhinovirus infection of primary HBECs and fibroblasts resulted in synergistic induction of basolateral IL-6 that was significantly abrogated by IL-1Ra. This study provides the first direct evidence of integrated IL-1 signalling within the EMTU to propagate inflammatory responses to viral infection.
1-12
Hill, Alison R.
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Donaldson, Jess E.
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Blume, Cornelia
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Smithers, Natalie
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Tezera, Liku
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Tariq, Kamran
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Dennison, Patrick
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Rupani, Hitasha
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Edwards, Matthew J.
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Howarth, Peter H.
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Grainge, Chris
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Davies, Donna E.
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Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f
Hill, Alison R.
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Donaldson, Jess E.
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Blume, Cornelia
aa391c64-8718-4238-906b-d6bb1551a07b
Smithers, Natalie
63ead01b-6515-4f82-a963-884f572af872
Tezera, Liku
c5598dbf-23a8-4934-96a4-7c783bf9e776
Tariq, Kamran
4de9ca91-e58a-49d7-970b-1b1cada17cf7
Dennison, Patrick
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Rupani, Hitasha
ed650f59-d273-46e9-ac34-0cd179f494ca
Edwards, Matthew J.
138adfc8-db80-445c-845f-8422fc7c9eb2
Howarth, Peter H.
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Grainge, Chris
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Davies, Donna E.
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Swindle, Emily J.
fe393c7a-a513-4de4-b02e-27369bd7e84f

Hill, Alison R., Donaldson, Jess E., Blume, Cornelia, Smithers, Natalie, Tezera, Liku, Tariq, Kamran, Dennison, Patrick, Rupani, Hitasha, Edwards, Matthew J., Howarth, Peter H., Grainge, Chris, Davies, Donna E. and Swindle, Emily J. (2016) IL-1alpha mediates cellular cross-talk in the airway epithelial mesenchymal trophic unit. Tissue Barriers, 4 (3), 1-12. (doi:10.1080/21688370.2016.1206378).

Record type: Article

Abstract

The bronchial epithelium and underlying fibroblasts form an epithelial mesenchymal trophic unit (EMTU) which controls the airway microenvironment. We hypothesised that cell-cell communication within the EMTU propagates and amplifies the innate immune response to respiratory viral infections.

EMTU co-culture models incorporating polarized (16HBE14o-) or differentiated primary human bronchial epithelial cells (HBECs) and fibroblasts were challenged with double-stranded RNA (dsRNA) or rhinovirus.

In the polarized EMTU model, dsRNA affected ionic but not macromolecular permeability or cell viability. Compared with epithelial monocultures, dsRNA-stimulated pro-inflammatory mediator release was synergistically enhanced in the basolateral compartment of the EMTU model, with the exception of IL-1alpha which was unaffected by the presence of fibroblasts. Blockade of IL-1 signalling with IL-1 receptor antagonist (IL-1Ra) completely abrogated dsRNA-induced basolateral release of mediators except CXCL10. Fibroblasts were the main responders to epithelial-derived IL-1 since exogenous IL-1alpha induced pro-inflammatory mediator release from fibroblast but not epithelial monocultures. Our findings were confirmed in a differentiated EMTU model where rhinovirus infection of primary HBECs and fibroblasts resulted in synergistic induction of basolateral IL-6 that was significantly abrogated by IL-1Ra. This study provides the first direct evidence of integrated IL-1 signalling within the EMTU to propagate inflammatory responses to viral infection.

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Submitted date: 18 May 2016
Accepted/In Press date: 21 June 2016
e-pub ahead of print date: 28 June 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 398588
URI: https://eprints.soton.ac.uk/id/eprint/398588
PURE UUID: 2b3a04d7-b500-4fb8-acbb-851fb60eb29b
ORCID for Alison R. Hill: ORCID iD orcid.org/0000-0001-5397-873X
ORCID for Cornelia Blume: ORCID iD orcid.org/0000-0001-6133-7318
ORCID for Liku Tezera: ORCID iD orcid.org/0000-0002-7898-6709
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991
ORCID for Emily J. Swindle: ORCID iD orcid.org/0000-0003-3644-7747

Catalogue record

Date deposited: 01 Aug 2016 08:20
Last modified: 03 Dec 2019 06:37

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Contributors

Author: Alison R. Hill ORCID iD
Author: Jess E. Donaldson
Author: Cornelia Blume ORCID iD
Author: Natalie Smithers
Author: Liku Tezera ORCID iD
Author: Kamran Tariq
Author: Patrick Dennison
Author: Hitasha Rupani
Author: Matthew J. Edwards
Author: Chris Grainge
Author: Donna E. Davies ORCID iD

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