- Title
- IL-1α mediates cellular cross-talk in the airway epithelial mesenchymal trophic unit
- Creator
- Hill, Alison R.; Donaldson, Jessica E.; Grainge, Christopher; Davies, Donna E.; Swindle, Emily J.; Blume, Cornelia; Smithers, Natalie; Tezera, Liku; Tariq, Kamran; Dennison, Patrick; Rupani, Hitasha; Edwards, Matthew J.; Howarth, Peter H.
- Relation
- Tissue Barriers Vol. 4, Issue 3
- Publisher Link
- http://dx.doi.org/10.1080/21688370.2016.1206378
- Publisher
- Taylor & Francis
- Resource Type
- journal article
- Date
- 2016
- Description
- The bronchial epithelium and underlying fibroblasts form an epithelial mesenchymal trophic unit (EMTU) which controls the airway microenvironment. We hypothesized 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-1α which was unaffected by the presence of fibroblasts. Blockade of IL-1 signaling 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-1α 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 signaling within the EMTU to propagate inflammatory responses to viral infection.
- Subject
- cross-talk; epithelial cells; fibroblasts; <i>in vitro</i> models of the airway; viral infection
- Identifier
- http://hdl.handle.net/1959.13/1327994
- Identifier
- uon:25787
- Identifier
- ISSN:2168-8370
- Rights
- © 2016 Alison R. Hill, Jessica E. Donaldson, Cornelia Blume, Natalie Smithers, Liku Tezera, Kamran Tariq, Patrick Dennison, Hitasha Rupani, Matthew J. Edwards, Peter H. Howarth, Christopher Grainge, Donna E. Davies, and Emily J. Swindle. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly properly cited. The moral rights of the names author(s) have been asserted.
- Language
- eng
- Full Text
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