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Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life.

JCI insight | 2016

Asthma is a chronic inflammatory airways disease that usually begins in early life and involves gene-environment interactions. Although most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Here, we report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma. We show that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and plays a role in airway remodeling, independent of inflammation. Furthermore, remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. When induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps to explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, we show that sADAM33-induced airway remodeling is reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma.

Pubmed ID: 27489884 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: G19/34
  • Agency: MRF, United Kingdom
    Id: MRF_MRF-009-0003-RG-HAITC
  • Agency: Medical Research Council, United Kingdom
    Id: G0800766
  • Agency: Medical Research Council, United Kingdom
    Id: G0800649
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL108907
  • Agency: Medical Research Council, United Kingdom
    Id: G0400473
  • Agency: Medical Research Council, United Kingdom
    Id: G0900453
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL110964
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Medical Research Council, United Kingdom
    Id: G0802804
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL095580

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