The Therapeutic Effect of Phosphopeptide P140 Attenuates Inflammation Induced by Uric Acid Crystals in Gout Arthritis Mouse Model.
MSU crystal-induced inflammation
autophagy
inflammasome
neutrophil
pain
peptide therapy
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
22 Nov 2022
22 Nov 2022
Historique:
received:
05
10
2022
revised:
17
11
2022
accepted:
18
11
2022
entrez:
11
12
2022
pubmed:
12
12
2022
medline:
15
12
2022
Statut:
epublish
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.
Identifiants
pubmed: 36496970
pii: cells11233709
doi: 10.3390/cells11233709
pmc: PMC9740613
pii:
doi:
Substances chimiques
Uric Acid
268B43MJ25
Phosphopeptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Region Grand-Est
ID : 2020
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
ID : [402530/2020-9] and [420350/2018-7]
Organisme : Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG)
ID : [APQ-03328-18]
Organisme : Instituto Serrapilheira
ID : Serra-1912-31552
Organisme : University of Strasbourg-CNRS-Inserm, IdEx Unistra
ID : ANR-10-IDEX-0002
Organisme : SFRI - STRAT'US project
ID : ANR-20-SFRI-0012
Organisme : Pro-Reitoria de Pesquisa da Universidade Federal de Minas Gerais -PRPq
ID : 2022
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-PRINT)
ID : 001
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