Figure 1

Simvastatin inhibits TLR8, but not TLR2, -4 or -5, signaling and is not reversed by GGPP in primary human monocytes. (A) Cells were incubated with 10 µg/mL simvastatin for 30 min and then stimulated with 10 ng/mL Pam3, 100 ng/mL LPS, 2 µg/mL R-848 or 10 ng/mL flagellin for 16 h. Supernatants were analyzed for TNF. Data pooled from four separate donors are shown as a percentage of the appropriate maximal response (*p < 0.0001). (B) Cell viability was measured by MTT assay. Data are pooled from four separate donors as a percentage of the appropriate maximal response. (C) Primary human monocytes were cultured in the presence of 10 µg/mL simvastatin ± 10 µmol/L GGPP for 30 min before stimulation with 2 µg/mL R-848. Supernatants were analyzed for TNF production. Data are representative of five separate experiments using five different donors. (D) Primary human monocytes were cultured in the presence of 0 or 10 µg/mL simvastatin ± 1 µmol/L mevalonate for 30 min before stimulation with R-848. Supernatants were analyzed for TNF production. Data are representative of four separate experiments using four different donors.