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: Murine macrophages (RAW264.7 cells) were stimulated with endotoxin, endotoxin plus MgSO4, or endotoxin plus MgSO4 plus PI3K inhibitor (LY294002 or wortmannin). Control groups were run simultaneously. After harvesting, we assayed the expression of inflammatory mediators, transcriptional factor nuclear factor κB (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 α (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 α (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 NF-κB 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 MgSO4 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 anti-inflammation effects of MgSO4.
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:Murine macrophages (RAW264.7 cells) were stimulated with endotoxin, endotoxin plus MgSO4, or endotoxin plus MgSO4 plus PI3K inhibitor (LY294002 or wortmannin). Control groups were run simultaneously. After harvesting, we assayed the expression of inflammatory mediators, transcriptional factor nuclear factor κB (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 α (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 α (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 NF-κB 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 MgSO4 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 anti-inflammation effects of MgSO4.
Authors: Juan R Muñoz-Castañeda; María V Pendón-Ruiz de Mier; Mariano Rodríguez; María E Rodríguez-Ortiz Journal: Int J Mol Sci Date: 2018-02-27 Impact factor: 5.923
Authors: Xin Yu; Pei-Pei Guan; Di Zhu; Yun-Yue Liang; Tao Wang; Zhan-You Wang; Pu Wang Journal: Front Mol Neurosci Date: 2018-05-30 Impact factor: 5.639