Inhibition of NO by pioglitazone is related to inhibition of p38 MAPK activity. A: A selective p38 MAPK inhibitor (SB203580), or a selective JNK inhibitor (SP600125), was added to microglia-enriched cultures 1 hr before LPS (1 μg/ml) exposure and, after 24 hrs, NO levels were measured. Only the p38 MAPK inhibitor prevented NO production. B: Pretreatment with pioglitazone inhibited LPS-induced phosphorylation of p38 MAPK in mesencephalic neuronal-microglia mixed cultures. Pioglitazone was added 1 hr before LPS treatment (1 μg/ml) and, after 30 mins, p38 MAPK was immunobloted. As shown in 3B, LPS increased phosphorylation of p38 MAPK, and pretreatment with pioglitazone inhibited this expression. Data presented are representative of three independent experiments (n = 3). (*p < 0.05 vs. control, ***p < 0.001 vs. control, #p < 0.05 vs. LPS).