Titre :

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

Auteur(s) :

Esnault, Stéphane [Auteur]
University of Wisconsin School of Medicine and Public Health
Kelly, Elizabeth A [Auteur]
Johnson, Sean H [Auteur]
DeLain, Larissa P [Auteur]
Haedt, Madeline J [Auteur]
Noll, Andrea L [Auteur]
Sandbo, Nathan [Auteur]
Jarjour, Nizar N [Auteur]

Titre de la revue :

Mediators of Inflammation

Nom court de la revue :

Mediators Inflamm

Numéro :

2019

Pagination :

7479107

Date de publication :

2019-02-17

ISSN :

1466-1861

Mot(s)-clé(s) en anglais :

Cells, Cultured
Cytokines
Eosinophilia
Eosinophils
Humans
Inflammasomes
Interleukin-1beta
Interleukin-5
Matrix Metalloproteinase 9

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

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 ...
Lire la suite >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.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Autres travaux scientifiques

Date de dépôt :

2023-10-23T10:06:03Z
2024-06-17T11:47:36Z