Cutting edge: Antimalarial drugs inhibit IFN-ß production through blockade of cyclic GMP-AMP synthase-DNA interaction.
J Immunol
; 194(9): 4089-93, 2015 May 01.
Article
em En
| MEDLINE
| ID: mdl-25821216
ABSTRACT
Type I IFN is strongly implicated in the pathogenesis of systemic autoimmune diseases, such as lupus, and rare monogenic IFNopathies, including Aicardi-Goutières syndrome. Recently, a new DNA-activated pathway involving the enzyme cyclic GMP-AMP synthase (cGAS) was described and potentially linked to Aicardi-Goutières syndrome. To identify drugs that could potentially inhibit cGAS activity, we performed in silico screening of drug libraries. By computational analysis, we identified several antimalarial drugs (AMDs) that were predicted to interact with the cGAS/dsDNA complex. Our studies validated that several AMDs were effective inhibitors of IFN-ß production and that they functioned by inhibiting dsDNA stimulation of cGAS. Because AMDs have been widely used in human diseases and have an excellent safety profile, our findings suggest new therapeutic strategies for the treatment of severe debilitating diseases associated with type I IFNs due to cGAS activation.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
DNA
/
Interferon beta
/
Antimaláricos
/
Nucleotidiltransferases
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2015
Tipo de documento:
Article