Figure 4

Geranylgeranylpyrophosphate (GGPP) restores the viability of synovial fibroblasts in the presence of statins. Synovial fibroblasts were cultured for 96 hours in the presence of 1, 3 or 10 μM lovastatin, atorvastatin or simvastatin supplemented with 5 μM farnesylpyrophosphate (FPP) or 5 μM GGPP, or neither FPP nor GGPP (control). XTT assays were performed on quadruplicate wells to determine the percentage cellular viability of treated in comparison with non-treated cultures. Each treatment was performed on two different synovial fibroblast lines. A representative experiment is shown. In a separate experiment, synovial fibroblasts were pretreated with 10 ng/ml tumor necrosis factor-α for 24 hours before the addition of 10 μM atorvastatin or simvastatin and 5 μM FPP or 5 μM GGPP. They were cultured for a further 96 hours before an XTT assay on quadruplicate wells.