ADAM33 in embryonic lungs
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.
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Official URL: http://thorax.bmj.com/cgi/reprint/60/suppl_2/ii4
Description/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.
| Item Type: | Article |
|---|---|
| Additional Information: | British Thoracic Society Winter Meeting 2005: Programme and Abstracts: Spoken Sessions |
| ISSN: | 0040-6376 (print) |
| Uncontrolled Keywords: | England, lung, publishing, time, London |
| Related URLs: | http://thorax.bmj.com/cgi/repr...uppl_2/ii4 |
| Subjects: | R Medicine > RB Pathology Q Science > QH Natural history > QH426 Genetics |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair |
| ePrint ID: | 59796 |
| URI: | http://eprints.soton.ac.uk/id/eprint/59796 |
| Deposited On: | 17 Mar 2009 |
| Last Modified: | 20 Apr 2012 13:51 |
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