Figure 4

AcLDL reversibly stimulates SR-A expression via activation of p38 MAPK. (A) Cultured resident MPM were pretreated, as indicated, with specific inhibitors of p38 [SB203580 (10 μM)], JNK [SP600125 (20 μM)] or ERK1/2 [PD98059 (10 μM)] for 20 minutes at 37°C. Cells were then treated with or without AcLDL (50 μg/ml) for 24 hrs at 37°C, and as indicated incubated without AcLDL for additional 72 hrs (Reverse). Cell lysates were prepared and SR-A protein expression quantified by immunoblotting. A representative immunoblot from a single experiment and the results (mean ± SEM) from at least three separate experiments are shown. * denotes significant difference (p < 0.05) from AcLDL treated control value (ANOVA with Dunnett's multiple comparison). (B) To determine whether AcLDL induces MAPK activation in SR-A dependent manner, MPM from wild type and SR-A-/- mice were cultured for 48 hrs and then incubated without or with M-CSF (25 ng/ml) or AcLDL (50 μg/ml) for 10 min. Cells lysates were prepared and phosphorylation of individual MAPKs detected by immunoblotting. A representative immunoblot from a single experiment and the results (mean ± SEM) from at least three separate experiments are shown. * denotes significant difference (p < 0.05) from untreated wild-type value (ANOVA with Dunnett's multiple comparison).