Induction of a disintegrin and metalloprotease 33 during embryonic lung development and the influence of IL-13 or maternal allergy
Induction of a disintegrin and metalloprotease 33 during embryonic lung development and the influence of IL-13 or maternal allergy
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.
ADAM33, embryonic/fetal, lung development, maternal allergy, environment gene interaction, geNorm analysis
590-597.e11
Haitchi, Hans Michael
68dadb29-305d-4236-884f-e9c93f4d78fe
Bassett, David J.P.
607bbbba-f4af-4e2f-bed2-e5978726354a
Bucchieri, Fabio
d5c6c38a-8b02-4a37-afb0-c272033cb0d2
Gao, Xiufeng
a5802cf9-a965-43fb-9297-98e1377e459c
Powell, Robert M.
884d6594-3f50-4be5-9516-d64b29dad63d
Hanley, Neil A.
bf03f7bb-f377-44fb-8344-0bb1ca8b2ef9
Wilson, David I.
1500fca1-7082-4271-95f4-691f1d1252a2
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
September 2009
Haitchi, Hans Michael
68dadb29-305d-4236-884f-e9c93f4d78fe
Bassett, David J.P.
607bbbba-f4af-4e2f-bed2-e5978726354a
Bucchieri, Fabio
d5c6c38a-8b02-4a37-afb0-c272033cb0d2
Gao, Xiufeng
a5802cf9-a965-43fb-9297-98e1377e459c
Powell, Robert M.
884d6594-3f50-4be5-9516-d64b29dad63d
Hanley, Neil A.
bf03f7bb-f377-44fb-8344-0bb1ca8b2ef9
Wilson, David I.
1500fca1-7082-4271-95f4-691f1d1252a2
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Haitchi, Hans Michael, Bassett, David J.P., Bucchieri, Fabio, Gao, Xiufeng, Powell, Robert M., Hanley, Neil A., Wilson, David I., Holgate, Stephen T. and Davies, Donna E.
(2009)
Induction of a disintegrin and metalloprotease 33 during embryonic lung development and the influence of IL-13 or maternal allergy.
Journal of Allergy and Clinical Immunology, 124 (3), .
(doi:10.1016/j.jaci.2009.06.026).
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.
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More information
Published date: September 2009
Keywords:
ADAM33, embryonic/fetal, lung development, maternal allergy, environment gene interaction, geNorm analysis
Organisations:
Human Genetics, Infection Inflammation & Immunity
Identifiers
Local EPrints ID: 69669
URI: http://eprints.soton.ac.uk/id/eprint/69669
ISSN: 0091-6749
PURE UUID: 19b280e6-eaeb-432a-a1ed-98b6ba06cf1c
Catalogue record
Date deposited: 27 Nov 2009
Last modified: 14 Mar 2024 02:47
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Contributors
Author:
David J.P. Bassett
Author:
Fabio Bucchieri
Author:
Xiufeng Gao
Author:
Robert M. Powell
Author:
Neil A. Hanley
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