Figure 4

Microglial p38α MAPK-dependent TNFα is involved in LPS-induced neuronal death. (A) TNFα levels in the conditioned media were measured at 24 h and 72 h after LPS addition. The TNFα response to LPS was significantly reduced in the p38α KO microglia/neuron co-cultures (***p < 0.0005; p38α WT+LPS vs. p38α KO+LPS). (B) Addition of a neutralizing antibody to TNFα in p38α WT microglia/neuron co-culture abolished LPS-induced neurotoxicity in a concentration-dependent manner, with significant protective effects at concentrations of 50 ng/ml and higher. The non-immune rabbit IgG control antibody at 5000 ng/ml had no protective effect (**p < 0.005 or ***p < 0.0005; compared to p38α WT+LPS; Bonferroni's multiple comparison test). (C) Addition of exogenous TNFα (5 ng/ml or 10 ng/ml) to the LPS-stimulated p38α KO microglia reduced neuronal survival. Compared to the p38α KO microglia stimulated with LPS alone, 5 ng/ml (*p < 0.05) and 10 ng/ml (**p < 0.005) TNFα significantly decreased neuronal survival (Bonferroni's multiple comparison test). Data represents 3-6 independent experiments.