Phosphoinositide 3-kinase/Akt pathway is involved in mediating the anti-inflammation effects of magnesium sulfate

Background: We sought to elucidate whether enhancing phosphoinositide 3-kinase (PI3K)/Akt activity is a crucial mechanism underlying the anti-inflammation effects of magnesium sulfate (MgSO4). Materials and methods: Murinemacrophages (RAW264.7 cells)were stimulatedwith endotoxin, endotoxin plus MgSO4, or endotoxin plusMgSO4 plus PI3K inhibitor (LY294002 orwortmannin). Control groups were run simultaneously. After harvesting, we assayed the expression of inflammatory mediators, transcriptional factor nuclear factor kB (NF-κB), and Akt. Results: MgSO4 significantly attenuated endotoxin-induced upregulation of inflammatory mediators and NF-κB, as macrophages treated with endotoxin plus MgSO4 had significantly lower tumor necrosis factor a (P =0.022), macrophage inflammatory protein 2 (P =0.040), phosphorylated (p)-NF-κB p65 (P =0.003) and p-inhibitor-κB (P <0.001) concentrations as well as lower NF-κB DNA binding (P =0.001) than macrophages treated with endotoxin alone. Moreover, macrophages treated with endotoxin plus MgSO4 plus LY294002 or wortmannin had significantly higher tumor necrosis factor a (P =0.013 and P <0.001), macrophage inflammatory protein 2 (P =0.023 and P =0.003), p-NF-κB p65 (P =0.006 and P <0.001), and p-inhibitor-κB (P =0.001 and P <0.001) concentrations, as well as higher NFκB DNA binding (P =0.038 and P =0.009), than macrophages treated with endotoxin plus MgSO4, suggesting that PI3K inhibitors reversed these effects of MgSO4. In contrast, macrophages treated with endotoxin plus MgSO4 had significantly higher p-Akt concentration than macrophages treated with endotoxin alone (P =0.004). Moreover, macrophages treated with endotoxin plus MgSO 4 also had significantly higher p-Akt concentration than macrophages treated with endotoxin plus MgSO4 plus LY294002 or wortmannin (P =0.004 and P <0.001). Conclusions: Enhancing PI3K/Akt activity is a crucial mechanism underlying the antiinflammation effects of MgSO4.