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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.

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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: 03 Dec 2019 02:07

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Contributors

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

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