title: Induction of a disintegrin and metalloprotease 33 during embryonic lung development and the influence of IL-13 or maternal allergy.
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.
  
  
  CONCLUSIONS
  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.
authors: Division of Infection Inflammation and Immunity, Roger Brooke Laboratory, School of Medicine, University of Southampton, Southampton, UK. hmha@soton.ac.uk
authors: Hans Michael
authors: HM
authors: Haitchi
authors: David J P
authors: DJ
authors: Bassett
authors: Fabio
authors: F
authors: Bucchieri
authors: Xiufeng
authors: X
authors: Gao
authors: Robert M
authors: RM
authors: Powell
authors: Neil A
authors: NA
authors: Hanley
authors: David I
authors: DI
authors: Wilson
authors: Stephen T
authors: ST
authors: Holgate
authors: Donna E
authors: DE
authors: Davies
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology; D018793:Interleukin-13 / Q000378:metabolism* / Q000494:pharmacology; D008168:Lung / Q000196:embryology* / Q000201:enzymology / Q000276:immunology; D051379:Mice; D009924:Organ Culture Techniques; D010047:Ovalbumin / Q000276:immunology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018793:Interleukin-13; D020033:Protein Isoforms; D012333:RNA, Messenger; D010047:Ovalbumin; D051722:ADAM Proteins; C450441:ADAM33 protein, human; C499183:Adam33 protein, mouse