The University of Southampton
University of Southampton Institutional Repository

The contribution of interleukin (IL)-4 and IL-13 to the epithelial-mesenchymal trophic unit in asthma

The contribution of interleukin (IL)-4 and IL-13 to the epithelial-mesenchymal trophic unit in asthma
The contribution of interleukin (IL)-4 and IL-13 to the epithelial-mesenchymal trophic unit in asthma
Interleukin (IL)-4 and IL-13 are key proinflammatory cytokines in asthma. Studies in transgenic mice show that both cytokines cause inflammation, but only IL-13 causes subepithelial fibrosis, a characteristic feature of asthma. We compared the in vitro profibrogenic effects of IL-4 and IL-13 using bronchial fibroblasts from asthmatic subjects. In the presence of transforming growth factor (TGF)-beta the cells transformed into contractile myofibroblasts and expressed alpha -smooth muscle actin and procollagen I. IL-4 and IL-13 also stimulated proliferation, but were relatively ineffective in promoting myofibroblast transformation. TGF-beta was more potent than the cytokines in stimulating release of endothelin-1 and vascular endothelial growth factor, whereas IL-4 and IL-13 were more potent stimuli for eotaxin release. Although neither IL-4 nor IL-13 induced profibrotic responses, both cytokines caused a corticosteroid-insensitive stimulation of TGF-beta 2 release from primary bronchial epithelial cells. These data indicate that epithelial activation by IL-13 or IL-4 plays a critical role in initiating remodeling through release of TGF-beta 2. TGF-beta 2 then activates the underlying myofibroblasts to secrete matrix proteins and smooth muscle and vascular mitogens to propagate remodeling changes into the submucosa. In contrast, direct activation of submucosal fibroblasts by IL-4 and IL-13 has a proinflammatory effect via eotaxin release and recruitment of eosinophils into the airways.
1044-1549
385-391
Richter, Audrey
5b4fb888-b3a7-4b81-a8a7-ffd2c046a196
Puddicombe, Sarah M.
fd8d76d1-203d-4f06-a7c2-678c946fb931
Lordan, James L.
15a9bdfb-bf61-4aea-a0f4-d83868eb39d0
Bucchieri, Fabio
3f85c9c8-2bc0-4fd0-b481-a03935fe3cb0
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Dent, Gordon
73559f2a-168a-4f3d-b478-f3838e77132f
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Richter, Audrey
5b4fb888-b3a7-4b81-a8a7-ffd2c046a196
Puddicombe, Sarah M.
fd8d76d1-203d-4f06-a7c2-678c946fb931
Lordan, James L.
15a9bdfb-bf61-4aea-a0f4-d83868eb39d0
Bucchieri, Fabio
3f85c9c8-2bc0-4fd0-b481-a03935fe3cb0
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Dent, Gordon
73559f2a-168a-4f3d-b478-f3838e77132f
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

Richter, Audrey, Puddicombe, Sarah M., Lordan, James L., Bucchieri, Fabio, Wilson, Susan J., Djukanovic, Ratko, Dent, Gordon, Holgate, Stephen T. and Davies, Donna E. (2001) The contribution of interleukin (IL)-4 and IL-13 to the epithelial-mesenchymal trophic unit in asthma. American Journal of Respiratory Cell and Molecular Biology, 25 (3), 385-391. (doi:10.1165/ajrcmb.25.3.4437).

Record type: Article

Abstract

Interleukin (IL)-4 and IL-13 are key proinflammatory cytokines in asthma. Studies in transgenic mice show that both cytokines cause inflammation, but only IL-13 causes subepithelial fibrosis, a characteristic feature of asthma. We compared the in vitro profibrogenic effects of IL-4 and IL-13 using bronchial fibroblasts from asthmatic subjects. In the presence of transforming growth factor (TGF)-beta the cells transformed into contractile myofibroblasts and expressed alpha -smooth muscle actin and procollagen I. IL-4 and IL-13 also stimulated proliferation, but were relatively ineffective in promoting myofibroblast transformation. TGF-beta was more potent than the cytokines in stimulating release of endothelin-1 and vascular endothelial growth factor, whereas IL-4 and IL-13 were more potent stimuli for eotaxin release. Although neither IL-4 nor IL-13 induced profibrotic responses, both cytokines caused a corticosteroid-insensitive stimulation of TGF-beta 2 release from primary bronchial epithelial cells. These data indicate that epithelial activation by IL-13 or IL-4 plays a critical role in initiating remodeling through release of TGF-beta 2. TGF-beta 2 then activates the underlying myofibroblasts to secrete matrix proteins and smooth muscle and vascular mitogens to propagate remodeling changes into the submucosa. In contrast, direct activation of submucosal fibroblasts by IL-4 and IL-13 has a proinflammatory effect via eotaxin release and recruitment of eosinophils into the airways.

Full text not available from this repository.

More information

Published date: 1 September 2001

Identifiers

Local EPrints ID: 27367
URI: https://eprints.soton.ac.uk/id/eprint/27367
ISSN: 1044-1549
PURE UUID: 282c64ce-267f-446c-b803-41bd2cd4a19b
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

Catalogue record

Date deposited: 28 Apr 2006
Last modified: 07 Aug 2019 00:54

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×