Figure 4
The p38α MAPK pathway is engaged in primary microglia and contributes to cytokine upregulation. Rat primary microglia were treated with either diluent (gray bars), stressor (either 1ng/ml LPS or 5 μM oligomeric Aβ1-42) in the absence of 069A (white bars), or stressor in the presence of 15 μM 069A (black bars). The LPS-induced increases in IL-1β (A) and TNFα (B) levels by rat primary microglia were significantly inhibited by the p38α inhibitor 069A. Similar results were obtained with a non-TLR ligand, Aβ1-42. LPS or Aβ also caused an increase in the phosphorylated (active) form of two p38α substrates, p-MK2 (C) and p-MSK1 (D), and phosphorylation of these substrates was blocked by the addition of 069A. Asterisk denotes significance (* = p < 0.05, ** = p < 0.01, or *** = p < 0.001) for stressor-stimulated microglia in the absence of 069A compared to stimulated microglia in the presence of 069A. Values with stimulus alone (white bars) were normalized to 100%. Data represent four independent experiments.