Background Peroxisome proliferator-activated receptor gamma (PPARγ) agonist has anti-inflammatory properties, which has known to reduce inflammatory cytokine production in RA. Cysteine-rich angiogenic inducer 61 (Cyr61) is associated with diseases related to chronic inflammation. Cyr61, pro-inflammatory factor, has been shown to be increased in the synovial tissues of patients with RA. However the action mechanisms between Cyr61 and PPARγ are unknown.
To determine the effects of peroxisome proliferator–activated receptorγ (PPARγ) agonists on tumour necrosis factor alpha (TNF-α)- induced of FLS invasiveness phenotype and Cystein -rich angiogenic inducer 61 (Cyr61) in Rheumatoid arthritis Fibroblast-like synoviocytes (RA-FLS).
Materials and methods FLS were cultured with TNF-α and Cyr61 in the presence or absence of PPARγ agonists. MMPs and CYR61 expression levels in the RA-FLS and culture medium were measured reverse transcriptase–polymerase chain reaction (RT-PCR) and western blotting. The migration and invasive phenotype of RA-FLS were determined by a scratch wound healing assay and the Boyden chamber assay.
Results Cyr61 protein was expressed on RA-FLS, and its expression was increased by TNFα. Moreover, Cyr61 directly promoted RA-FLS migration (p<0.01) and invasion (p<0.01) compared to the untreated RA-FLS. RSG significantly decreased TNFα-induced Cyr61 expression. Furthermore, not only did RSG inhibit TNFα induced RA-FLS migration distance (p<0.01) and invasion (p=0.018), but also decreased Cyr61 treated RA-FLS invasion (p<0.01).
Conclusion Our result show that PPARγ agonist may have beneficial effects on migration and invasion of RA-FLS via down-regulation of Cyr61. Therefore, PPARγ agonist could be a potential treatment of RA.
- Rheumatoid arthritis
- Cysteinerich angiogenic inducer 61
- Peroxisome proliferator-activated receptor gamma
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