TY - JOUR T1 - Arsenic Trioxide Induces Apoptosis of Fibroblast-like Synoviocytes and Represents Antiarthritis Effect in Experimental Model of Rheumatoid Arthritis JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.100299 SP - jrheum.100299 AU - Yifang Mei AU - Yining Zheng AU - Hui Wang AU - Juan Gao AU - Dianxin Liu AU - Yanping Zhao AU - Zhiyi Zhang Y1 - 2010/10/01 UR - http://www.jrheum.org/content/early/2010/09/27/jrheum.100299.abstract N2 - 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-κB (NF-κB) was then detected by ELISAand 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 RAFLS. It suppressed the DNA-binding activity and mRNA expression level of NF-κB, probably by inhibiting tumor necrosis factor-α-induced activation of NF-κB. 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 RAFLS through NF-κB 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. ER -