Figure 5

Microglia deficient in p38α MAPK show a reduced cytokine response to LPS. Primary microglia isolated from either p38α conditional KO mice (p38α^-/-; black bar) or wild-type littermates (p38α^+/+; white bar) were stimulated with 1ng/ml LPS for either 18 hrs (for cytokine measurements) or 1 hr (for western blots). There was a significant reduction in the IL-1β (A) and TNFα (B) response to LPS in microglia from the p38α KO mice compared to wild-type microglia. (C) There was also substantially reduced LPS-induced phosphorylation of p38α substrates MSK1 and MK2 in p38α^-/^- microglia compared to p38α^+/+ microglia. The loss of p38α in the KO microglia was confirmed by little or no reactivity with a phospho-p38α/β antibody, a p38α/β antibody and a p38α-selective antibody. Asterisk denotes significance (*** = p < 0.001) for p38α^+/+ microglia (white bar) compared to p38α^-/- microglia (black bar). Responses of the wild-type microglia were normalized to 100%. Data represent three independent experiments.