Figure 1.

Statins conferred cellular protection on airway epithelial cells against pneumolysin. (A) Human Bronchial Epithelial 1 (HBE1) cells were treated with 1 μM simvastatin for 24 hours. Simvastatin was then removed from the culture, and cells were further challenged with 500 ng/ml pneumolysin (PLY) for 4 hours. Cells were cultured for 10 days to determine the CFUs. (B–E) Cellular ATP release was quantified to determine cell viability. Asterisks indicate significant statistical difference versus matching control with one-way ANOVA and Dunnet’s post test. Error bars represent SEM of three to five experiments. (B) HBE1 cells were pretreated with indicated doses of simvastatin for 24 hours and then challenged with PLY for 4 hours. (C) HBE1 cells were pretreated with 1 μM simvastatin for 24 hours and then challenged with the indicated doses of PLY for 4 hours. (D) Normal HBE (NHBE) cells were pretreated with the indicated doses of simvastatin for 24 hours and then challenged with 500 ng/ml of PLY for 4 hours. (E) HBE1 cells were pretreated with 0.1 or 10 μM pravastatin for 24 hours and then challenged with 400 ng/ml PLY for 4 hours. (F) C57BL/6 mice, 10 to 12 weeks old, were injected intraperitoneally with 20 mg/kg simvastatin for 6 days and then injected intratracheally by 200 ng/ml PLY or PBS control for overnight. Lungs were fixed and sectioned for hematoxylin and eosin staining for histopathology. Data are representative images from four mice per group. Scale bar: 100 μm. EtOH, ethanol; ns, not significant; *P < 0.05; **P < 0.01; ***P < 0.001.