The University of Southampton
University of Southampton Institutional Repository

Signal transducer and activator of transcription 6 (STAT-6) expression and function in asthmatic bronchial epithelium

Signal transducer and activator of transcription 6 (STAT-6) expression and function in asthmatic bronchial epithelium
Signal transducer and activator of transcription 6 (STAT-6) expression and function in asthmatic bronchial epithelium
Background: Asthma is associated with increased production of IL-4 and IL-13. 
Objective: Because many of the effects of these cytokines are mediated by activation of signal transducer and activator of transcription 6 (STAT-6), we investigated expression and function of this transcription factor in the airways.
Methods: STAT-6 expression was investigated through use of immunohistochemistry or RT-PCR applied to bronchial biopsy specimens or brushings from normal control or asthmatic subjects. STAT-6 function was investigated by means of Western blotting and ELISA applied to primary epithelial cell cultures. 
Results: Immunohistochemistry revealed that the bronchial epithelium was the major site of STAT-6 expression, both cytoplasmic and nuclear staining being observed. The level of STAT-6 expression in subjects with mild asthma (median [range] percent epithelial staining, 3.4% [0% to 16.0%]; N = 14) did not differ significantly from that in normal controls (4.7% [0.0% to 20.0%]; N = 11); however, in subjects with severe asthma, epithelial STAT-6 expression (13.7% [4.8% to 25.7%]; N = 9) was increased in comparison with subjects with mild asthma and normal controls (P < .05). RT-PCR analysis showed that epithelial STAT-6 expression was heterogeneous and comprised both full-length STAT-6 and the dominant-negative variant that lacks the SH2 domain. Treatment of primary cultures of bronchial epithelial cells with IL-4 resulted in STAT-6 phosphorylation and stimulation of IL-8 secretion; however, no difference in the responses of epithelial cells was observed between normal (n = 12) and asthmatic (n = 14) donors.

Conclusion: These data demonstrate expression and activation of STAT-6 in normal and asthmatic bronchial epithelium. The activity of this transcription factor is likely to play a key role in mediating the responses of the bronchial epithelium to TH2 cytokines that are characteristic of the asthmatic phenotype.
0091-6749
832-838
Mullings, Rebecca E.
9d2b0339-fa90-4689-ba5e-66d5649c3ee8
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Puddicombe, Sarah M.
fd8d76d1-203d-4f06-a7c2-678c946fb931
Lordan, James L.
15a9bdfb-bf61-4aea-a0f4-d83868eb39d0
Bucchieri, Fabio
3f85c9c8-2bc0-4fd0-b481-a03935fe3cb0
Djukanovic´, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Harper, Steven
86ae7dff-e8ad-4458-8fde-eafd0ab3d1cf
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Mullings, Rebecca E.
9d2b0339-fa90-4689-ba5e-66d5649c3ee8
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Puddicombe, Sarah M.
fd8d76d1-203d-4f06-a7c2-678c946fb931
Lordan, James L.
15a9bdfb-bf61-4aea-a0f4-d83868eb39d0
Bucchieri, Fabio
3f85c9c8-2bc0-4fd0-b481-a03935fe3cb0
Djukanovic´, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Harper, Steven
86ae7dff-e8ad-4458-8fde-eafd0ab3d1cf
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

Mullings, Rebecca E., Wilson, Susan J., Puddicombe, Sarah M., Lordan, James L., Bucchieri, Fabio, Djukanovic´, Ratko, Howarth, Peter H., Harper, Steven, Holgate, Stephen T. and Davies, Donna E. (2001) Signal transducer and activator of transcription 6 (STAT-6) expression and function in asthmatic bronchial epithelium. Journal of Allergy and Clinical Immunology, 108 (5), 832-838. (doi:10.1067/mai.2001.119554).

Record type: Article

Abstract

Background: Asthma is associated with increased production of IL-4 and IL-13. 
Objective: Because many of the effects of these cytokines are mediated by activation of signal transducer and activator of transcription 6 (STAT-6), we investigated expression and function of this transcription factor in the airways.
Methods: STAT-6 expression was investigated through use of immunohistochemistry or RT-PCR applied to bronchial biopsy specimens or brushings from normal control or asthmatic subjects. STAT-6 function was investigated by means of Western blotting and ELISA applied to primary epithelial cell cultures. 
Results: Immunohistochemistry revealed that the bronchial epithelium was the major site of STAT-6 expression, both cytoplasmic and nuclear staining being observed. The level of STAT-6 expression in subjects with mild asthma (median [range] percent epithelial staining, 3.4% [0% to 16.0%]; N = 14) did not differ significantly from that in normal controls (4.7% [0.0% to 20.0%]; N = 11); however, in subjects with severe asthma, epithelial STAT-6 expression (13.7% [4.8% to 25.7%]; N = 9) was increased in comparison with subjects with mild asthma and normal controls (P < .05). RT-PCR analysis showed that epithelial STAT-6 expression was heterogeneous and comprised both full-length STAT-6 and the dominant-negative variant that lacks the SH2 domain. Treatment of primary cultures of bronchial epithelial cells with IL-4 resulted in STAT-6 phosphorylation and stimulation of IL-8 secretion; however, no difference in the responses of epithelial cells was observed between normal (n = 12) and asthmatic (n = 14) donors.

Conclusion: These data demonstrate expression and activation of STAT-6 in normal and asthmatic bronchial epithelium. The activity of this transcription factor is likely to play a key role in mediating the responses of the bronchial epithelium to TH2 cytokines that are characteristic of the asthmatic phenotype.

Full text not available from this repository.

More information

Published date: 2001
Additional Information: Mechanisms of Allergy

Identifiers

Local EPrints ID: 27280
URI: https://eprints.soton.ac.uk/id/eprint/27280
ISSN: 0091-6749
PURE UUID: 6b9a3f2a-7431-4981-8f69-bfb0da463e3f
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: 24 May 2019 00:39

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.

×