Abstract
Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that primarily manifests as persistent synovitis and progressive joint destruction. Imatinib exhibited a therapeutic effect in murine collagen-induced arthritis (CIA) via selective inhibition tyrosine kinases. The second-generation tyrosine kinase inhibitor dasatinib exhibits more durable hematological and cytogenetic effects and more potency compared to imatinib. However, the effect of dasatinib on CIA is poorly understood. The present study investigated the treatment effect of dasatinib on autoimmune arthritis. We demonstrated that dasatinib alleviated arthritis symptoms and histopathological destruction in CIA mice. Dasatinib treatment inhibited the production of proinflammatory cytokines including IL-1β, TNF-α, and IL-6, and promoted the production of the anti-inflammatory cytokine IL-10. Dasatinib treatment also suppressed the expression of anti-mouse CII antibodies including total IgG, IgG1, IgG2, and IgG2b, in CIA mice. We further demonstrated that dasatinib inhibited the migration and proliferation of fibroblast-like synoviocytes (FLS) from RA patients and promoted FLS apoptosis. The mRNA expression of MMP13, VEGF, FGF, and DKK1 was down-regulated in FLS treated with dasatinib. Our findings suggest that dasatinib exhibited treatment effects on CIA mice and that FLS are an important target cell of dasatinib treatment in autoimmune arthritis.
Highlights
Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune inflammatory disease that causes chronic inflammation in joints and subsequent cartilage destruction and bone loss
The present study investigated the treatment effect of dasatinib on collagen-induced arthritis (CIA) mice
The alleviation of arthritis symptoms and histopathological destruction was observed in CIA mice treated with dasatinib
Summary
Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune inflammatory disease that causes chronic inflammation in joints and subsequent cartilage destruction and bone loss. RA is a common disease that leads to musculoskeletal disability. Small joints such as those in the hands and feet are always involved in RA, and larger joints such as the knees are frequently affected. FLS contribute to inflammation and joint destruction. The synovium is a quiescent relatively acellular structure in normal people. Many factors such as Dasatinib Treats Autoimmune Arthritis high levels of cytokines, growth factors, and infiltrating inflammatory cells, stimulate the synovium in RA, and it becomes hyperplastic and invasive [4, 5]. The targeting of FLS may be an effective strategy for RA treatment
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