关键词: 羧胺三唑, 类风湿关节炎, 成纤维样滑膜细胞, TNF-α

Abstract: Objective To investigate the effect of carboxyamidotriazole (CAI) on TNF-α-induced activation of fibroblast-like synoviocyte(FLS) derived from patients with rheumatoid arthritis (RA). Methods FLS were isolated and cultured from synovial tissues of RA patients and identified by immunofluorescence. The cells were stimulated with TNF-α in the presence or absence of various concentrations of CAI. Cell proliferation was assessed by CCK-8 assay. The contents of IL-6, IL-8 and MMP-3 in the culture supernatant were measured by ELISA. NF-κB p65 DNA-binding activity in the nuclear extracts was detected using TransAM kit. Results TNF-α stimulation significantly promoted the proliferation of RA-FLS, upregulated the secretion of IL-6, IL-8 and MMP-3, and enhanced the DNA-binding activity of NF-κB p65. Treatment with 10 μmol/L CAI inhibited TNF-α-induced FLS proliferation (P＜0.05), IL-6 and MMP-3 secretion (P＜0.01), as well as NF-κB p65 activation (P＜0.01). Furthermore, 20, 30 and 40 μmol/L CAI significantly suppressed all the TNF-α-induced elevations in the detected parameters (P＜0.01). Conclusions CAI may attenuate TNF-α-induced proliferation and production of IL-6, IL-8 and MMP-3 in RA-FLS through suppressing NF-κB activation, suggesting that CAI has the potential to be developed as a therapeutic agent for RA.

Key words: carboxyamidotriazole, rheumatoid arthritis, fibroblast-like synoviocytes, TNF-α