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J Allergy Clin Immunol. 2009 Sep;124(3):590-7, 597.e1-11. doi: 10.1016/j.jaci.2009.06.026. Epub 2009 Aug 8.

Induction of a disintegrin and metalloprotease 33 during embryonic lung development and the influence of IL-13 or maternal allergy.

Author information

  • 1Division of Infection Inflammation and Immunity, Roger Brooke Laboratory, School of Medicine, University of Southampton, Southampton, UK. hmha@soton.ac.uk

Abstract

BACKGROUND:

Asthma pathogenesis involves gene and environmental interactions. A disintegrin and metalloprotease 33 (ADAM33)/Adam33 is a susceptibility gene for asthma and bronchial hyperresponsiveness in human beings and mice. ADAM33 is almost exclusively expressed in mesenchymal cells, including mesenchymal progenitors in developing lungs.

OBJECTIVE:

Because maternal allergy is a risk factor for asthma, we hypothesized that an allergic environment affects ADAM33/Adam33 expression during human and mouse lung development.

METHODS:

Human embryonic/fetal lung (HEL) tissues were collected from first-trimester terminations of pregnancy. These were processed immediately or used for explant culture +/- IL-13. MF1 mice or ovalbumin-sensitized A/J mice (Bronchial hyperresponsivness (Bhr)1/Adam33 locus-positive) were time-mated and challenged with ovalbumin (A/J mice only) during pregnancy. Lungs were harvested at different times during gestation and post partum. ADAM33/Adam33 expression was analyzed by using reverse transcriptase quantitative polymerase chain reaction and Western blotting.

RESULTS:

ADAM33 mRNA was detectable in HELs in the pseudoglandular stage of development and showed a significant increase from 7 to 9 weeks postconception. IL-13 significantly suppressed ADAM33 mRNA in HEL explants. In developing murine lungs, Adam33 mRNA and protein expression increased significantly in the early pseudoglandular stage and showed another large increase post partum. In A/J mice, maternal allergy significantly suppressed Adam33 mRNA in lungs of newborn pups, whereas processed Adam33 protein increased and several smaller isoforms were detected.

CONCLUSION:

Adam33/Adam33 shows 2 significant increments in expression during lung morphogenesis, suggesting important developmental regulation. The ability of maternal allergy or exogenous IL-13 to suppress Adam33/ADAM33 mRNA but enhance Adam33 processing suggests a gene-environment interaction that may be relevant for asthma pathogenesis.

PMID:
19665773
[PubMed - indexed for MEDLINE]
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