The Therapeutic Effect of Phosphopeptide P140 Attenuates Inflammation Induced by Uric Acid Crystals in Gout Arthritis Mouse Model.
Fiche publication
Date publication
novembre 2022
Journal
Cells
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MULLER Sylviane
Tous les auteurs :
Galvão I, Mastrippolito D, Talamini L, Aganetti M, Rocha V, Verdot C, Mendes V, de Oliveira VLS, Braga AD, Martins VD, de Faria AMC, Amaral FA, Georgel P, Vieira AT, Muller S
Lien Pubmed
Résumé
Gout is a painful form of inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints. The aim of this study was to investigate the effect of peptide P140 on the inflammatory responses in crystal-induced mouse models of gout and cell models including MSU-treated human cells. Injection of MSU crystals into the knee joint of mice induced neutrophil influx and inflammatory hypernociception. Injection of MSU crystals subcutaneously into the hind paw induced edema and increased pro-inflammatory cytokines levels. Treatment with P140 effectively reduced hypernociception, the neutrophil influx, and pro-inflammatory cytokine levels in these experimental models. Furthermore, P140 modulated neutrophils chemotaxis in vitro and increased apoptosis pathways through augmented caspase 3 activity and reduced NFκB phosphorylation. Moreover, P140 increased the production of the pro-resolving mediator annexin A1 and decreased the expression of the autophagy-related ATG5-ATG12 complex and HSPA8 chaperone protein. Overall, these findings suggest that P140 exerts a significant beneficial effect in a neutrophilic inflammation observed in the model of gout that can be of special interest in the design of new therapeutic strategies.
Mots clés
MSU crystal-induced inflammation, autophagy, inflammasome, neutrophil, pain, peptide therapy
Référence
Cells. 2022 11 22;11(23):