Sphingosine Kinase 1 Plays an Important Role in Atorvastatin-Mediated Anti-Inflammatory Effect against Acute Lung Injury

Figure 4

Atorvastatin attenuated cyclic stretch- (CS-) mediated cytokine generation from mouse-isolated endothelial cells, but SphK1 knockout reversed this effect. The isolated ECs were seeded on Flexcell plate and cyclic stretched (CS) (18% elongation, 0.5 Hz, 4 hours). After cyclic stretch, the medium was harvested for ELISA. CS significantly increased cytokine release in the WT endothelial medium. These cytokines include IL6, KC, MIP-1α, MIP-2, and MCP-1, but not IL-1β. The CS-mediated cytokine release in WT mouse endothelial medium was significantly attenuated by pretreatment of atorvastatin; CS-mediated cytokine concentrations were significantly higher in SphK1^-/- mouse endothelial medium than those in WT mice. Moreover, SphK1 knockout reversed the inhibitory effect of atorvastatin in cytokine generation in endothelial cells. (, ).

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