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Publication : Itaconate reduces proliferation and migration of fibroblast-like synoviocytes and ameliorates arthritis models.

First Author  Tada M Year  2024
Journal  Clin Immunol Volume  264
Pages  110255 PubMed ID  38763433
Mgi Jnum  J:351323 Mgi Id  MGI:7663044
Doi  10.1016/j.clim.2024.110255 Citation  Tada M, et al. (2024) Itaconate reduces proliferation and migration of fibroblast-like synoviocytes and ameliorates arthritis models. Clin Immunol 264:110255
abstractText  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.
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