Interferon-ß therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome.
Sci Signal
; 5(225): ra38, 2012 May 22.
Article
em En
| MEDLINE
| ID: mdl-22623753
Interferon-ß (IFN-ß) is widely used to treat multiple sclerosis (MS), and its efficacy was demonstrated in the setting of experimental autoimmune encephalomyelitis (EAE), an animal model of MS; however, IFN-ß is not effective in treating all cases of MS. Here, we demonstrate that signaling by IFNAR (the shared receptor for IFN-α and IFN-ß) on macrophages inhibits activation of Rac1 and the generation of reactive oxygen species (ROS) through suppressor of cytokine signaling 1 (SOCS1). The inhibition of Rac1 activation and ROS generation suppressed the activity of the Nod-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome, which resulted in attenuated EAE pathogenicity. We further found that two subsets of EAE could be defined on the basis of their dependency on the NLRP3 inflammasome and that IFN-ß was not an effective therapy when EAE was induced in an NLRP3 inflammasome-independent fashion. Thus, our study demonstrates a previously uncharacterized signaling pathway that is involved in the suppression of EAE by IFN-ß and characterizes NLRP3-independent EAE, which cannot be treated with IFN-ß.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Interferon beta
/
Encefalomielite Autoimune Experimental
/
Receptor de Interferon alfa e beta
/
Inflamassomos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Sci Signal
Assunto da revista:
CIENCIA
/
FISIOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos