Figure 2. Reversal of inhibitory effect of simvastatin on KB cells by co-treatment with downstream metabolites of HMG-CoA reductase. (A) Inhibitory effects of simvastatin (10^–6 M) on KB cells were reversed by co-treatment with mevalonate (10^–4 M) or GGPP (5 x 10^–6 M), but not with FPP (5 x 10^–6 M). Data are expressed as means ± SD (n = 4). *P < 0.001 vs. control (treated with IL-1). (B) Schematic representation of the mevalonate pathway. Statins block conversion of HMG-CoA to mevalonate. This leads to reduced synthesis of cholesterol and decreased prenylation of proteins such as small GTPases. Isopentenyl-PP, isopentenyl pyrophosphate; Geranyl-PP, geranyl pyrophosphate.