Therapeutic potential of the FPR2/ALX agonist AT-01-KG in the resolution of articular inflammation.
Pharmacol Res
; 165: 105445, 2021 03.
Article
en En
| MEDLINE
| ID: mdl-33493655
ABSTRACT
The resolution of inflammation is a dynamic process, characterized by the biosynthesis of pro-resolving mediators, including the lipid Lipoxin A4 (LXA4). LXA4 acts on the N-formyl peptide receptor 2 (FPR2/ALX) to mediate anti-inflammatory and pro-resolving effects. In order to exploit the therapeutic potential of endogenous LXA4 in the context of inflammation we have recently developed synthetic LXA4 mimetics (sLXms) including a dimethyl-imidazole-containing FPR2/ALX agonist designated AT-01-KG. Here, we have investigated the effect of treatment with AT-01-KG in established models of articular inflammation. In a model of gout, mice were injected with MSU crystals and treated with AT-01-KG at the peak of inflammatory response. The treatment decreased the number of neutrophils in the knee exudate, an effect which was accompanied by low levels of myeloperoxidase, CXCL1 and IL-1ß in periarticular tissue. AT-01-KG treatment led to reduced tissue damage and hypernociception. The effects of AT-01-KG on neutrophil accumulation were not observed in MSU treated FPR2/3-/-mice. Importantly, AT-01-KG induced resolution of articular inflammation by increasing neutrophil apoptosis and subsequent efficient efferocytosis. In a model of antigen-induced arthritis, AT-01-KG treatment also attenuated inflammatory responses. These data suggest that AT-01-KG may be a potential new therapy for neutrophilic inflammation of the joints.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Cartílago Articular
/
Supresores de la Gota
/
Receptores de Formil Péptido
/
Gota
Límite:
Animals
Idioma:
En
Revista:
Pharmacol Res
Asunto de la revista:
FARMACOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Brasil