Atorvastatin Represses the Angiotensin 2-Induced Oxidative Stress and Inflammatory Response in Dendritic Cells via the PI3K/Akt/Nrf 2 Pathway
Figure 4
The PI3K/Akt/Nrf 2 pathway is involved in the atorvastatin-mediated inhibition of Ang 2-induced cellular responses. After pretreatment with PBS and either the Nrf 2 activator SUL (10 μM) or the PI3K inhibitor LY294002 (100 nM) for 1 h, BMDCs were incubated for 24 h with Ang 2 (100 nM) alone, atorvastatin (10 μM) alone, or Ang 2 (100 nM) and atorvastatin (10 μM) combined. We observed markers of oxidative stress and inflammation in the BMDCs. (a) Intracellular ROS levels were measured with flow cytometry using DCFH-DA. (b) SOD activity and (c) MDA levels were measured by ELISA kits. (d) Expression of the cell-surface markers CD40, CD83, CD80, and CD86 as determined by flow cytometry (). (e) Expression of the cytokines in BMDCs analyzed by ELISA (). (f) Atorvastatin decreased the ability of BMDCs to activate T cells. BMDCs were cultured with 100 nM Ang 2 for 48 h in the absence or presence of 10 μM atorvastatin. Cells were harvested and then incubated with 1 × 105 T cells in a 96-well plate at a ratio of 1 : 10 (BMDCs : T cells) for 5 days. For the final 18 h of incubation, 20 μL of diluted BrdU was added to the appropriate wells (). The data are shown as the means ± (SD) (); versus control; # versus Ang 2 group; versus Ang 2 + atorvastatin group.
