Inhibition of Toll-like receptor-mediated inflammation in vitro and in vivo by a novel benzoxaborole.
J Pharmacol Exp Ther
; 344(2): 436-46, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-23192653
ABSTRACT
Pro-inflammatory cytokines play a critical role in the development of autoimmune and inflammatory diseases. Targeting the cytokine environment has proven efficient for averting inflammation. In this study, we reported that 6-[4-(aminomethyl)-2-chlorophenoxyl]benzo[c][1,2]oxaborol-1(3H)-ol (AN3485), a benzoxaborole analog, inhibited TLR2-, TLR3-, TLR4-, and TLR5-mediated TNF-α, IL-1ß, and IL-6 release from human PBMCs and isolated monocytes with IC(50) values ranging from 18 to 580 nM, and the inhibition was mediated at the transcriptional level. Topical administration of AN3485 significantly reduced PMA-induced contact dermatitis and oxazolone-induced delayed-type hypersensitivity in mice, indicating its capability of penetrating skin and potential topical application in skin inflammation. Oral administration of AN3485 showed dose-dependent suppression of LPS-induced TNF-α and IL-6 production in mice with an ED(90) of 30 mg/kg. Oral AN3485, 35 mg/kg, twice a day, suppressed collagen-induced arthritis in mice over a 20-day period. The potent anti-inflammatory activity in in vitro and in vivo disease models makes AN3485 an attractive therapeutic lead for a variety of cutaneous and systemic inflammatory diseases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artritis
/
Compuestos de Boro
/
Antiinflamatorios no Esteroideos
/
Dermatitis Alérgica por Contacto
/
Compuestos Bicíclicos Heterocíclicos con Puentes
/
Hipersensibilidad a las Drogas
/
Receptores Toll-Like
/
Hipersensibilidad Tardía
Tipo de estudio:
Etiology_studies
Idioma:
En
Revista:
J Pharmacol Exp Ther
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos