ADAM-8, a metalloproteinase, drives acute allergen-induced airway inflammation

Geneviève Paulissen1, Natacha Rocks, Maud M Guéders

  • 1Laboratory of Tumor and Development Biology, GIGA-Research (GIGA-I3 and GIGA-cancer), University of Liege and CHU of Liege, Sart-Tilman, Belgium.

Insights

A disintegrin and metalloproteinase-8 (ADAM-8) promotes allergen-induced airway inflammation by increasing dendritic cell (DC) recruitment and chemokine production. Inhibiting ADAM-8 reduces inflammation in a mouse asthma model.

Area of Science:

  • Immunology
  • Respiratory Medicine
  • Molecular Biology

Background:

  • Asthma involves complex inflammatory pathways, with proteinases playing a key role.
  • A disintegrin and metalloproteinases (ADAMs) are implicated in inflammatory processes.
  • ADAM-8's specific role in allergic airway inflammation requires further investigation.

Purpose of the Study:

  • To investigate the expression and function of ADAM-8 in a mouse model of allergen-induced airway inflammation.
  • To determine the impact of ADAM-8 inhibition on inflammatory cell recruitment and mediator production.

Main Methods:

  • Utilized a mouse model of allergen-induced airway inflammation.
  • Assessed ADAM-8 expression in lung tissue and isolated dendritic cells (DCs).
  • Employed anti-ADAM-8 antibody treatment and ADAM-8 knockout mice (ADAM-8(-/-)) to evaluate functional roles.
  • Quantified inflammatory cells in bronchoalveolar lavage fluid (BALF) and peribronchial areas.
  • Measured levels of chemokines CCL11 and CCL22.

Main Results:

  • ADAM-8 expression was significantly increased in the lungs of allergen-exposed mice.
  • Treatment with anti-ADAM-8 antibody or using ADAM-8(-/-) mice reduced acute airway inflammation.
  • ADAM-8 depletion led to a significant decrease in CD11c(+) lung dendritic cells (DCs).
  • Lower levels of CCL11 and CCL22 were observed in mice with reduced ADAM-8 activity.

Conclusions:

  • ADAM-8 promotes allergen-induced acute airway inflammation.
  • ADAM-8 appears to facilitate inflammation by enhancing DC recruitment and the production of CCL11 and CCL22.
  • Targeting ADAM-8 may represent a therapeutic strategy for allergic airway diseases.

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