Fig. 4.
CD36-TLR4-TLR6 signaling induces microglial inflammatory responses that promote neurotoxicity. (a-b) Production of nitric oxide in (a) wild type, Tlr2−/−, Tlr4−/−, Tlr6−/−, Cd36−/− and (b) Md2−/− microglia stimulated with Aβ1-42 (10 μM) or LPS (100ng/ml) for 24 hours. (c) Reactive oxygen species production in microglia of the indicated genotype stimulated with Aβ1-42 (10 μM) for 45 min. Data are the mean ± s.d. of triplicate samples and are representative of an experimental n of 3. *P<0.005. (d) IL-1β and (e) RANTES mRNA measured by QRT-PCR in wild type, Tlr4−/−, Tlr6−/−, Myd88−/− or Trif−/− macrophages stimulated with Aβ1-42 (10 μM, 6h). Data are the mean ± s.d. of triplicate samples and are representative of an experimental n of 2-3. *P<0.05. (f) CAD mouse neuronal cells co-cultured with wild type, Tlr2−/−, Tlr4−/− and Tlr6−/− microglial cells stimulated with Aβ1-42 (10 μM, 72 h) and stained with anti-neuronal class III beta tubulin Ab (green) and DAPI nuclear stain (blue). Quantification of % neuronal survival is shown at right.