Suberoylanilide Hydroxamic Acid, an Inhibitor of Histone Deacetylase, Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

Here, we explored the effects of suberoylanilide hydroxamic acid (SAHA) on the viability and apoptosis of rheumatoid arthritis of fibroblast-like synoviocytes (rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS)). FLS obtained from RA patients were treated with SAHA. SAHA significantly inhibited the viability of RA FLS in a concentration-dependent manner up to 5 µM. SAHA-treated FLS showed a significant increase in the percentage of apoptosis and the expression and activity of caspase-3 and higher intracellular ROS levels. N-acetyl-l-cysteine (NAC) pretreatment significantly attenuated SAHA-induced apoptosis, decreasing the percentage of apoptosis by about 60 %. A significant decline in phosphorylated IκBα and nuclear factor kappa B (NF-κB) p65 and concomitant increase in total IκBα were shown in SAHA-treated FLS. Additionally, the levels of anti-apoptotic Bcl-2 proteins (Bcl-xL and Mcl-1) were significantly reduced by SAHA. Collectively, SAHA induces apoptosis of RA FLS, at least partially, through generation of ROS and suppression of NF-κB activation and Bcl-xL and Mcl-1 expression.

[Effects of arsenic trioxide on the autoimmunity and survival time in BXSB lupus mice].

OBJECTIVE: To investigate the effect of arsenic trioxide (ATO) on the autoimmunity and survival time in BXSB lupus mice. METHODS: The model BXSB lupus mice were randomly divided into two groups equally, the ATO treated group and the control group, 17 in each group. Mice in the ATO group were given intraperitoneal injection of ATO at the daily dose of 0.4 mg/kg, once every other day for 105 days or 90 days, respectively, and the observation lasted for 210 days. The survival time between the two groups was compared; the serum levels of anti-dsDNA and IgG were detected by enzyme-linked immunosorbent assay (ELISA), and the interferon-gamma (IFN-gamma) mRNA expression in renal and spleen tissue were measured by reverse transcriptase polymerase chain reaction (RT-PCR) technique. RESULTS: Till the 210th day, the total number of death was 8 in the ATO treated group and 13 in the control group, comparison between the two groups showed significantly different (chi2 = 4.20, P < 0.05). The mean OD value of serum anti-dsDNA antibody was lower in the ATO group (0.392 +/- 0.087) than that in the control group (0.566 +/- 0.080, P < 0.001). The serum level of IgG on day 105 in the ATO group was significantly lower than that in the control group and before treatment (P < 0.05). The expression of IFN-gamma mRNA in spleen tissue and renal tissue in the ATO group and the control group was 0.540 +/- 0.300 and 0.338 +/- 0.163, 2.320 +/- 0.522 and 0.588 +/- 0.104 (P < 0.05 and P < 0.01 respectively). CONCLUSION: ATO can prolong the survival time of BXSB lupus mice, decrease the peripheral level of anti-dsDNA antibody and IgG expression, inhibit the over-expression of IFN-gamma mRNA in spleen and kidney tissues.