Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation.

Détails

ID Serval
serval:BIB_368EADC3F807
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation.
Périodique
Journal of Biological Chemistry
Auteur(s)
Harris J., Hartman M., Roche C., Zeng S.G., O'Shea A., Sharp F.A., Lambe E.M., Creagh E.M., Golenbock D.T., Tschopp J., Kornfeld H., Fitzgerald K.A., Lavelle E.C.
ISSN
1083-351X (Electronic)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2011
Volume
286
Numéro
11
Pages
9587-9597
Langue
anglais
Résumé
Autophagy is a key regulator of cellular homeostasis that can be activated by pathogen-associated molecules and recently has been shown to influence IL-1β secretion by macrophages. However, the mechanisms behind this are unclear. Here, we describe a novel role for autophagy in regulating the production of IL-1β in antigen-presenting cells. After treatment of macrophages with Toll-like receptor ligands, pro-IL-1β was specifically sequestered into autophagosomes, whereas further activation of autophagy with rapamycin induced the degradation of pro-IL-1β and blocked secretion of the mature cytokine. Inhibition of autophagy promoted the processing and secretion of IL-1β by antigen-presenting cells in an NLRP3- and TRIF-dependent manner. This effect was reduced by inhibition of reactive oxygen species but was independent of NOX2. Induction of autophagy in mice in vivo with rapamycin reduced serum levels of IL-1β in response to challenge with LPS. These data demonstrate that autophagy controls the production of IL-1β through at least two separate mechanisms: by targeting pro-IL-1β for lysosomal degradation and by regulating activation of the NLRP3 inflammasome.
Mots-clé
Adaptor Proteins, Vesicular Transport/genetics, Adaptor Proteins, Vesicular Transport/metabolism, Animals, Anti-Bacterial Agents/pharmacology, Antigen-Presenting Cells/cytology, Antigen-Presenting Cells/metabolism, Autophagy/drug effects, Autophagy/physiology, Carrier Proteins/genetics, Carrier Proteins/metabolism, Cells, Cultured, Female, Interleukin-1beta/genetics, Interleukin-1beta/secretion, Ligands, Lipopolysaccharides/pharmacology, Lysosomes/genetics, Lysosomes/metabolism, Macrophages/cytology, Macrophages/metabolism, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, NADPH Oxidase, Sirolimus/pharmacology, Toll-Like Receptors/genetics, Toll-Like Receptors/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/09/2011 10:00
Dernière modification de la notice
20/08/2019 14:24
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