Matrix Metalloproteinase-9-Dependent Release of IL-1 by Human Eosinophils - Université de Lille
Article Dans Une Revue Mediators of Inflammation Année : 2019

Matrix Metalloproteinase-9-Dependent Release of IL-1 by Human Eosinophils

Elizabeth A Kelly
  • Fonction : Auteur
Sean H Johnson
  • Fonction : Auteur
Larissa P Delain
  • Fonction : Auteur
Madeline J Haedt
  • Fonction : Auteur
Andrea L Noll
  • Fonction : Auteur
Nathan Sandbo
  • Fonction : Auteur
Nizar N Jarjour
  • Fonction : Auteur

Résumé

Asthma is often associated with airway eosinophilia, and therapies targeting eosinophils are now available to treat severe eosinophilic asthma. Eosinophilic asthma is often due to a type-2 immune response and production of IL-5, which leads to eosinophilopiesis and recruitment of mature eosinophils in the airways. A concomitant type-2 and type-17 response has been reported in some individuals. IL-17 may be enhanced by IL-1 production and can lead to neutrophilic inflammation. In fact, both eosinophilic and neutrophilic (mixed granulocytic) inflammation are simultaneously present in a large population of patients with asthma. In monocyte/macrophage cell populations, release of mature IL-1 occurs via toll-like receptor ligand-induced activation of the inflammasome. Within the inflammasome, a cascade of events leads to the activation of caspase-1, which cleaves pro-IL-1 protein into a mature, releasable, and active form. We have demonstrated that eosinophils can release IL-1 in a Toll-like receptor ligand-independent fashion. The objective of this study was to determine the mechanisms underlying the production and maturation of IL-1 in cytokine-activated eosinophils. Using eosinophils from circulating blood and from bronchoalveolar lavage fluid after an airway allergen challenge, the present study demonstrates that cytokine-activated eosinophils express and release a bioactive form of IL-1 with an apparent size less than the typical 17 kDa mature form produced by macrophages. Using a zymography approach and pharmacological inhibitors, we identified matrix metalloproteinase-9 (MMP-9) as a protease that cleaves pro-IL-1 into a ~15 kDa form and allows the release of IL-1 from cytokine-activated eosinophils. Therefore, we conclude that activated eosinophils produce MMP-9, which causes the release of IL-1 in an inflammasome/caspase-1-independent manner. The production of IL-1 by eosinophils may be a link between the eosinophilic/type-2 immune response and the neutrophilic/type-17 immune response that is often associated with a more severe and treatment-refractory type of asthma.
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hal-04614265 , version 1 (17-06-2024)

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Stéphane Esnault, Elizabeth A Kelly, Sean H Johnson, Larissa P Delain, Madeline J Haedt, et al.. Matrix Metalloproteinase-9-Dependent Release of IL-1 by Human Eosinophils. Mediators of Inflammation, 2019, Mediators of Inflammation, 2019, pp.7479107. ⟨10.1155/2019/7479107⟩. ⟨hal-04614265⟩

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