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

Figure 1

Atorvastatin attenuated VILI-mediated lung permeability but SphK1 knockout reversed this effect. WT and SphK1^-/- were treated with atorvastatin overnight as described in Materials and Methods. The next day, the mice underwent high tidal volume ventilation (40 ml/kg, 65 breaths/min, 4 hours). After ventilation, the mouse BAL and lung were harvested for protein, cellular, and histology analysis. (a, b) Compared to spontaneously breathing control mice, HT significantly induced both protein and cells in BAL. Atorvastatin treatment attenuated the HT-mediated induction of protein and cells in BAL. Compared to WT mice, HT-induced SphK1^-/- mice had more protein and cell infiltration in the BAL. However, SphK1 knockout significantly abolished the atorvastatin-mediated anti-inflammatory effect in SphK1^-/- mice. (c, d) Compared to WT mice, HT-induced SphK1^-/- mice had significantly more cell filtration and alveolar structure damage with higher lung injury scores. Moreover, SphK1 knockout reversed atorvastatin-mediated cell filtration inhibitory effect on WT mice (, ).

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