David Fong, Pascal Grégoire-Gélinas, Alexandre P. Cheng, Tal Mezheritsky, Marc Lavertu
, Sachiko Sato et Caroline D. Hoemann
Article de revue (2017)
 Document en libre accès dans PolyPublie et chez l'éditeur officiel |
|
Libre accès au plein texte de ce document Version officielle de l'éditeur Conditions d'utilisation: Creative Commons: Attribution (CC BY) Télécharger (825kB) |
Abstract
Chitosan is a family of glucosamine and N-acetyl glucosamine polysaccharides with poorly understood immune modulating properties. Here, functional U937 macrophage responses were analyzed in response to a novel library of twenty chitosans with controlled degree of deacetylation (DDA, 60-98%), molecular weight (1 to >100 kDa), and acetylation pattern (block vs. random). Specific chitosan preparations (10 or 190 kDa 80% block DDA and 3, 5, or 10 kDa 98% DDA) either induced macrophages to release CXCL10 and IL-1ra at 5-50 mug/mL, or activated the inflammasome to release IL-1beta and PGE2 at 50-150 mug/mL. Chitosan induction of these factors required lysosomal acidification. CXCL10 production was preceded by lysosomal rupture as shown by time-dependent co-localization of galectin-3 and chitosan and slowed autophagy flux, and specifically depended on IFN-beta paracrine activity and STAT-2 activation that could be suppressed by PGE2. Chitosan induced a type I IFN paracrine response or inflammasome response depending on the extent of lysosomal rupture and cytosolic foreign body invasion. This study identifies the structural motifs that lead to chitosan-driven cytokine responses in macrophages and indicates that lysosomal rupture is a key mechanism that determines the endogenous release of either IL-1ra or IL-1beta.
Mots clés
- Acetylation
- Chemokine CXCL12/metabolism
- Chitosan/chemistry/*pharmacology
- Dinoprostone/metabolism
- Humans
- Inflammasomes/*metabolism
- Interferon Type I/*metabolism
- Interleukin 1 Receptor Antagonist Protein/metabolism
- Interleukin-1beta/metabolism
- Lysosomes/drug effects/*pathology
- Macrophages/drug effects/*metabolism
- Proton Magnetic Resonance Spectroscopy
- U937 Cells
- *Chitin/chitosan
- *Immunomodulation
- *Inflammasome
- *Macrophage
- *Type 1 interferon
| Département: |
Département de génie chimique Institut de génie biomédical |
|---|---|
| Centre de recherche: | GRSTB - Centre de recherche en sciences et technologies biomédicales |
| Organismes subventionnaires: | Canadian Institutes of Health Research, Fonds de recherche du Quebec - Sante, Fonds de recherche du Quebec - Nature et technologies, CRSNG / NSERC Summer Scholarship |
| Numéro de subvention: | MOP 303615-BME, 22341 |
| URL de PolyPublie: | https://publications.polymtl.ca/4868/ |
| Titre de la revue: | Biomaterials (vol. 129) |
| Maison d'édition: | Elsevier |
| DOI: | 10.1016/j.biomaterials.2017.03.022 |
| URL officielle: | https://doi.org/10.1016/j.biomaterials.2017.03.022 |
| Date du dépôt: | 16 août 2021 15:04 |
| Dernière modification: | 09 avr. 2025 01:36 |
| Citer en APA 7: | Fong, D., Grégoire-Gélinas, P., Cheng, A. P., Mezheritsky, T., Lavertu, M., Sato, S., & Hoemann, C. D. (2017). Lysosomal rupture induced by structurally distinct chitosans either promotes a type 1 IFN response or activates the inflammasome in macrophages. Biomaterials, 129, 127-138. https://doi.org/10.1016/j.biomaterials.2017.03.022 |
|---|---|
Statistiques
Total des téléchargements à partir de PolyPublie
Téléchargements par année
Provenance des téléchargements
Dimensions
Actions réservées au personnel
|
Afficher document |
