Inflammatory role of ASC in antigen-induced arthritis is independent of caspase-1, NALP-3, and IPAF.
Détails
ID Serval
serval:BIB_ADD4073A9A53
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Inflammatory role of ASC in antigen-induced arthritis is independent of caspase-1, NALP-3, and IPAF.
Périodique
Journal of Immunology
ISSN
1550-6606[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
183
Numéro
6
Pages
4003-4012
Langue
anglais
Résumé
Because IL-1beta plays an important role in inflammation in human and murine arthritis, we investigated the contribution of the inflammasome components ASC, NALP-3, IPAF, and caspase-1 to inflammatory arthritis. We first studied the phenotype of ASC-deficient and wild-type mice during Ag-induced arthritis (AIA). ASC(-/-) mice showed reduced severity of AIA, decreased levels of synovial IL-1beta, and diminished serum amyloid A levels. In contrast, mice deficient in NALP-3, IPAF, or caspase-1 did not show any alteration of joint inflammation, thus indicating that ASC associated effects on AIA are independent of the classical NALP-3 or IPAF inflammasomes. Because ASC is a ubiquitous cytoplasmic protein that has been implicated in multiple cellular processes, we explored other pathways through which ASC may modulate inflammation. Ag-specific proliferation of lymph node and spleen cells from ASC-deficient mice was significantly decreased in vitro, as was the production of IFN-gamma, whereas IL-10 production was enhanced. TCR ligation by anti-CD3 Abs in the presence or absence of anti-CD28 Abs induced a reduction in T cell proliferation in ASC(-/-) T cells compared with wild-type ones. In vivo lymph node cell proliferation was also significantly decreased in ASC(-/-) mice, but no effects on apoptosis were observed either in vitro or in vivo in these mice. In conclusion, these results strongly suggest that ASC modulates joint inflammation in AIA through its effects on cell-mediated immune responses but not via its implication in inflammasome formation.
Mots-clé
Animals, Antigens/toxicity, Apoptosis Regulatory Proteins/deficiency, Arthritis, Experimental/etiology, Arthritis, Experimental/pathology, Calcium-Binding Proteins/deficiency, Carrier Proteins/genetics, Caspase 1/deficiency, Cell Proliferation, Cytoskeletal Proteins/physiology, Inflammation/etiology, Joint Diseases/pathology, Lymph Nodes/pathology, Mice, Mice, Knockout, Multiprotein Complexes/immunology, Spleen/pathology
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/10/2009 15:04
Dernière modification de la notice
20/08/2019 16:17