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ADAM33 in embryonic lungs

ADAM33 in embryonic lungs
ADAM33 in embryonic lungs
Rationale: ADAM33 is an asthma susceptibility gene with polymorphic variation that is strongly associated with asthma and bronchial hyperresponsiveness ( Van Eerdewegh et al. Nature 2002;418:426–30[CrossRef][Medline]). Single nucleotide polymorphisms (SNPs) in ADAM33 also predict impaired lung function in COPD ( van Diemen et al. Am J Respir Crit Care Med 2005;172:329–33[Abstract/Free Full Text]) and in young children ( Simpson et al. Am J Respir Crit Care Med 2005;172:55–60[Abstract/Free Full Text]). To study the link between maternal atopy and development of asthma, we postulated that ADAM33 is expressed during embryonic lung development and is affected by Th2 cytokines.
Methods: Mouse lungs were harvested at embryonic day (ED) 11–19 and human embryonic lungs (HEL) (7–10 weeks) were collected following the Polkinghorne Committee guidelines after informed consent and ethical approval. Lung explants were cultured in vitro for 3–18 days±interleukin (IL)-13. Samples were processed for mRNA, protein, and image analysis.
Results: ADAM33 mRNA increased during embryonic development in mouse and human lungs. ADAM33 splice variants were detected in HELs but the ß-isoform and the metalloprotease domain were rare. Western blotting confirmed the presence of multiple isoforms of ADAM33. Immunomicroscopy showed ADAM33 around alpha smooth muscle actin ({alpha}SMA) positive tubular structures within the undifferentiated mesenchyme. In vitro, ADAM33 and {alpha}SMA mRNA expression in ED12 lung explants cultured with IL-13 were increased after 48 hours (p = 0.015) and 72 hours (p = 0.026) compared with lungs cultured in medium alone. HELs cultured for 6, 12, and 18 days in the presence of IL-13 showed cystic phenotypic changes compared with medium alone.
Conclusion: The expression of ADAM33 in developing embryonic lungs and its interaction with IL-13 suggests a key role in airway modelling that may contribute to the pathogenesis of chronic lung disease.
England, lung, publishing, time, London
0040-6376
p.ii22
Haitchi, H.M.
68dadb29-305d-4236-884f-e9c93f4d78fe
Bucchieri, F.
830cf621-3e39-42ab-b0ea-7d5dc43bf032
Powell, R.M.
360c7ec9-8cc4-4684-a810-97623f0e8232
Hanley, N.A.
ac5bcdcc-51dd-4f2c-ad06-fef6c1d50ebd
Wilson, D.I.
1500fca1-7082-4271-95f4-691f1d1252a2
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, D.E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Haitchi, H.M.
68dadb29-305d-4236-884f-e9c93f4d78fe
Bucchieri, F.
830cf621-3e39-42ab-b0ea-7d5dc43bf032
Powell, R.M.
360c7ec9-8cc4-4684-a810-97623f0e8232
Hanley, N.A.
ac5bcdcc-51dd-4f2c-ad06-fef6c1d50ebd
Wilson, D.I.
1500fca1-7082-4271-95f4-691f1d1252a2
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, D.E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

Haitchi, H.M., Bucchieri, F., Powell, R.M., Hanley, N.A., Wilson, D.I., Holgate, S.T. and Davies, D.E. (2005) ADAM33 in embryonic lungs. Thorax, 60 (Supplement 2), p.ii22.

Record type: Article

Abstract

Rationale: ADAM33 is an asthma susceptibility gene with polymorphic variation that is strongly associated with asthma and bronchial hyperresponsiveness ( Van Eerdewegh et al. Nature 2002;418:426–30[CrossRef][Medline]). Single nucleotide polymorphisms (SNPs) in ADAM33 also predict impaired lung function in COPD ( van Diemen et al. Am J Respir Crit Care Med 2005;172:329–33[Abstract/Free Full Text]) and in young children ( Simpson et al. Am J Respir Crit Care Med 2005;172:55–60[Abstract/Free Full Text]). To study the link between maternal atopy and development of asthma, we postulated that ADAM33 is expressed during embryonic lung development and is affected by Th2 cytokines.
Methods: Mouse lungs were harvested at embryonic day (ED) 11–19 and human embryonic lungs (HEL) (7–10 weeks) were collected following the Polkinghorne Committee guidelines after informed consent and ethical approval. Lung explants were cultured in vitro for 3–18 days±interleukin (IL)-13. Samples were processed for mRNA, protein, and image analysis.
Results: ADAM33 mRNA increased during embryonic development in mouse and human lungs. ADAM33 splice variants were detected in HELs but the ß-isoform and the metalloprotease domain were rare. Western blotting confirmed the presence of multiple isoforms of ADAM33. Immunomicroscopy showed ADAM33 around alpha smooth muscle actin ({alpha}SMA) positive tubular structures within the undifferentiated mesenchyme. In vitro, ADAM33 and {alpha}SMA mRNA expression in ED12 lung explants cultured with IL-13 were increased after 48 hours (p = 0.015) and 72 hours (p = 0.026) compared with lungs cultured in medium alone. HELs cultured for 6, 12, and 18 days in the presence of IL-13 showed cystic phenotypic changes compared with medium alone.
Conclusion: The expression of ADAM33 in developing embryonic lungs and its interaction with IL-13 suggests a key role in airway modelling that may contribute to the pathogenesis of chronic lung disease.

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More information

Published date: December 2005
Additional Information: British Thoracic Society Winter Meeting 2005: Programme and Abstracts: Spoken Sessions
Keywords: England, lung, publishing, time, London

Identifiers

Local EPrints ID: 59796
URI: http://eprints.soton.ac.uk/id/eprint/59796
ISSN: 0040-6376
PURE UUID: af5f29de-f238-4489-b590-68a5269fe627
ORCID for H.M. Haitchi: ORCID iD orcid.org/0000-0001-8603-302X
ORCID for D.E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

Catalogue record

Date deposited: 17 Mar 2009
Last modified: 23 Jul 2022 01:50

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Contributors

Author: H.M. Haitchi ORCID iD
Author: F. Bucchieri
Author: R.M. Powell
Author: N.A. Hanley
Author: D.I. Wilson
Author: S.T. Holgate
Author: D.E. Davies ORCID iD

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