Itaconate reduces proliferation and migration of fibroblast-like synoviocytes and ameliorates arthritis models.
Clin Immunol
; 264: 110255, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38763433
ABSTRACT
Fibroblast-like synoviocytes (FLS) play critical roles in rheumatoid arthritis (RA). Itaconate (ITA), an endogenous metabolite derived from the tricarboxylic acid (TCA) cycle, has attracted attention because of its anti-inflammatory, antiviral, and antimicrobial effects. This study evaluated the effect of ITA on FLS and its potential to treat RA. ITA significantly decreased FLS proliferation and migration in vitro, as well as mitochondrial oxidative phosphorylation and glycolysis measured by an extracellular flux analyzer. ITA accumulates metabolites including succinate and citrate in the TCA cycle. In rats with type II collagen-induced arthritis (CIA), intra-articular injection of ITA reduced arthritis and bone erosion. Irg1-deficient mice lacking the ability to produce ITA had more severe arthritis than control mice in the collagen antibody-induced arthritis. ITA ameliorated CIA by inhibiting FLS proliferation and migration. Thus, ITA may be a novel therapeutic agent for RA.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Artritis Experimental
/
Artritis Reumatoide
/
Succinatos
/
Movimiento Celular
/
Proliferación Celular
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Fibroblastos
/
Sinoviocitos
Límite:
Animals
Idioma:
En
Revista:
Clin Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón