PT  - JOURNAL ARTICLE
AU  - Akio Morinobu
AU  - Biao Wang
AU  - Jun Liu
AU  - Shinichi Yoshiya
AU  - Masahiro Kurosaka
AU  - Shunichi Kumagai
TI  - Trichostatin A cooperates with Fas-mediated signal to induce apoptosis in rheumatoid arthritis synovial fibroblasts.
DP  - 2006 Jun 01
TA  - The Journal of Rheumatology
PG  - 1052--1060
VI  - 33
IP  - 6
4099  - http://www.jrheum.org/content/33/6/1052.short
4100  - http://www.jrheum.org/content/33/6/1052.full
SO  - J Rheumatol2006 Jun 01; 33
AB  - OBJECTIVE: To clarify the effects of trichostatin A (TSA), a histone deacetylase inhibitor, on the growth and survival of rheumatoid arthritis synovial fibroblasts (RA-SF). METHODS: Cell viability was assessed using a WST-8 assay and direct cell counting. Apoptosis was detected by annexin V staining on a flow cytometer. Protein and mRNA expression was determined by Western blotting, flow cytometry, and RT-PCR. RESULTS: TSA suppressed cell growth of RA-SF in a dose-dependent manner, as determined by WST-8 assay and direct cell counting. Other histone deacetylase inhibitors also showed inhibitory effects on RA-SF proliferation. TSA upregulated p21(WAF1/CIP1) cell cycle inhibitor, suggesting that cell cycle arrest is involved in the reduction of cell numbers. In addition, TSA cooperated with Fas-induced pathway to induce cell death, determined by WST-8 assay and annexin V staining. TSA reduced FLICE inhibitory protein (FLIP) expression but not Bcl-2, Bcl-XL, and Fas expression, indicating that the synergistic effect may be through downregulation of FLIP. CONCLUSION: TSA has antirheumatic effects on RA-SF and might be a potential therapeutic tool for the treatment of RA.