The University of Southampton
University of Southampton Institutional Repository

IL-13 receptor ? 2: a regulator of IL-13 and IL-4 signal transduction in primary human fibroblasts

IL-13 receptor ? 2: a regulator of IL-13 and IL-4 signal transduction in primary human fibroblasts
IL-13 receptor ? 2: a regulator of IL-13 and IL-4 signal transduction in primary human fibroblasts
BACKGROUND: IL-13 and IL-4 share many functional properties as a result of their use of a common receptor complex comprising IL-13 receptor ? 1 (IL-13R?1) and IL-4 receptor alpha (IL-4R?). The nonsignaling receptor IL-13 receptor alpha 2 (IL-13?2) binds IL-13 with high affinity and specificity and is believed to be a decoy receptor for IL-13.
OBJECTIVE: We sought to examine the inhibitory effects of soluble and membrane-bound IL-13R?2 on IL-13- and IL-4-mediated effects.
METHODS: Primary human fibroblasts were grown from endobronchial biopsy specimens obtained from volunteers. Upregulation of IL-13R?2 mRNA was measured by means of RT-PCR, and the level of surface expression was measured by means of FACS.
RESULTS: We found that a recombinant soluble form of IL-13R?2 blocked the effects of IL-13, but not IL-4, in fibroblasts in vitro. However, we found that the transmembrane form of IL-13R?2 could attenuate both IL-13 and IL-4 responses, even though the response to TNF-alpha was unaffected. Furthermore, we found that IL-13?2 became associated with IL-4R? in the presence of IL-4. Addition of a blocking antibody to the extracellular domain of IL-13R?2 restored responses of both IL-13 and IL-4.
CONCLUSION: The ability of IL-13R?2 to regulate IL-4 was previously unrecognized in primary airway cells. These data reveal a novel role for IL-13R?2 as a negative regulator of both IL-13 and IL-4 signaling in human bronchial fibroblasts.
CLINICAL IMPLICATIONS: It appears that IL-13R?2 might be a powerful suppressor of TH2-mediated responses and thus represents a potential therapeutic target for the treatment of asthma.
allergy, cytokine receptors, signal transduction
0091-6749
858-865
Andrews, Allison-Lynn
4ddaec43-0f43-40cd-a191-aa53b0b30f16
Nasir, Tosia
55ff599c-8eb3-440e-ab7e-4b729bc15e6b
Bucchieri, Fabio
d5c6c38a-8b02-4a37-afb0-c272033cb0d2
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Andrews, Allison-Lynn
4ddaec43-0f43-40cd-a191-aa53b0b30f16
Nasir, Tosia
55ff599c-8eb3-440e-ab7e-4b729bc15e6b
Bucchieri, Fabio
d5c6c38a-8b02-4a37-afb0-c272033cb0d2
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

Andrews, Allison-Lynn, Nasir, Tosia, Bucchieri, Fabio, Holloway, John W., Holgate, Stephen T. and Davies, Donna E. (2006) IL-13 receptor ? 2: a regulator of IL-13 and IL-4 signal transduction in primary human fibroblasts. Journal of Allergy and Clinical Immunology, 118 (4), 858-865. (doi:10.1016/j.jaci.2006.06.041).

Record type: Article

Abstract

BACKGROUND: IL-13 and IL-4 share many functional properties as a result of their use of a common receptor complex comprising IL-13 receptor ? 1 (IL-13R?1) and IL-4 receptor alpha (IL-4R?). The nonsignaling receptor IL-13 receptor alpha 2 (IL-13?2) binds IL-13 with high affinity and specificity and is believed to be a decoy receptor for IL-13.
OBJECTIVE: We sought to examine the inhibitory effects of soluble and membrane-bound IL-13R?2 on IL-13- and IL-4-mediated effects.
METHODS: Primary human fibroblasts were grown from endobronchial biopsy specimens obtained from volunteers. Upregulation of IL-13R?2 mRNA was measured by means of RT-PCR, and the level of surface expression was measured by means of FACS.
RESULTS: We found that a recombinant soluble form of IL-13R?2 blocked the effects of IL-13, but not IL-4, in fibroblasts in vitro. However, we found that the transmembrane form of IL-13R?2 could attenuate both IL-13 and IL-4 responses, even though the response to TNF-alpha was unaffected. Furthermore, we found that IL-13?2 became associated with IL-4R? in the presence of IL-4. Addition of a blocking antibody to the extracellular domain of IL-13R?2 restored responses of both IL-13 and IL-4.
CONCLUSION: The ability of IL-13R?2 to regulate IL-4 was previously unrecognized in primary airway cells. These data reveal a novel role for IL-13R?2 as a negative regulator of both IL-13 and IL-4 signaling in human bronchial fibroblasts.
CLINICAL IMPLICATIONS: It appears that IL-13R?2 might be a powerful suppressor of TH2-mediated responses and thus represents a potential therapeutic target for the treatment of asthma.

This record has no associated files available for download.

More information

Published date: October 2006
Keywords: allergy, cytokine receptors, signal transduction

Identifiers

Local EPrints ID: 44312
URI: http://eprints.soton.ac.uk/id/eprint/44312
ISSN: 0091-6749
PURE UUID: 3aeb9fb7-ac45-404a-a7d2-d0d33a1cb164
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

Catalogue record

Date deposited: 23 Feb 2007
Last modified: 16 Mar 2024 02:57

Export record

Altmetrics

Contributors

Author: Allison-Lynn Andrews
Author: Tosia Nasir
Author: Fabio Bucchieri
Author: Donna E. Davies ORCID iD

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 http://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.

×