期刊
JOURNAL OF RHEUMATOLOGY
卷 38, 期 1, 页码 36-43出版社
J RHEUMATOL PUBL CO
DOI: 10.3899/jrheum.100299
关键词
RHEUMATOID ARTHRITIS; ARSENIC TRIOXIDE; APOPTOSIS SIGNAL TRANSDUCTION
类别
资金
- National Natural Science Foundation of China [30872336]
- Natural Science Foundation of Hei Longjiang province [ZD200814-02, D2007-83]
Objective. Recent studies have demonstrated that rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) proliferate as fiercely as tumor cells. Induction of apoptosis in RA FLS therefore provides a new approach for the inhibition of joint destruction. Arsenic trioxide (As2O3) was reported to be an effective apoptosis inducer in a variety of cell types. We investigated the possible effect of As2O3 on apoptosis induction of RA FLS and the mechanisms involved in this process. Methods. Apoptosis was determined by flow cytometric analysis, terminal deoxynucleotide transferase-mediated dUTP nick end-labeling, and transmission electron microscopy. The activity and messenger RNA (mRNA) expression of nuclear factor-kappa B (NF-kappa B) was then detected by ELISA and real-time polymerase chain reaction, respectively. Activities of caspase-3 and caspase-8 were evaluated using luminogenic substrates. The effect of As2O3 on the morphology of rats with collagen-induced arthritis was evaluated under a light microscope after H&E staining. Results. As2O3 significantly enhanced the apoptosis of RA FLS. It suppressed the DNA-binding activity and mRNA expression level of NF-kappa B, probably by inhibiting tumor necrosis factor-alpha-induced activation of NF-kappa B. As2O3 treatment significantly increased the activity of both caspase-3 and caspase-8. Morphological analysis revealed histological recovery in the synovial membrane. Synovial hyperplasia and inflammation in the joints were effectively inhibited. Conclusion. As2O3 represents an apoptotic effect on RA FLS through NF-kappa B signaling pathway, and this process is mediated by the activation of caspase cascade. Treatment with As2O3 significantly improved the pathologic changes of collagen-induced arthritis and may have potential for treatment of RA. (First Release Oct 1 2010: J Rheumatol 2011;38:36-43; doi:10.3899/jrheum.100299)
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