Microglial apolipoprotein E and astroglial apolipoprotein J expression in vitro:: opposite effects of lipopolysaccharide

Apolipoprotein E (apoE) and apoJ are lipid carriers produced in the brain primarily by glial cells. A variety of glial-activating stimuli induce a parallel upregulation of both apolipoproteins expression in vivo and in vitro . To further characterize the cell type and mechanisms by which apoE and apoJ expression are upregulated in activated glia, mixed glial cultures from neonatal rat cortex were treated with the endotoxin lipopolysaccharide (LPS). LPS induced dose-dependent increases in apoJ and decreases in apoE expression and secretion with maximum effects at 1-10 ng/mL and 0.1-1 mug/mL, respectively. Experiments with enriched astroglial and microglial cultures demonstrated that apoE and apoJ expression are predominantly microglial and astroglial, respectively. Given the pivotal role that nuclear factor-kappaB (NF-kappaB) plays in glial activation, we assessed its possible role in mediating apoE and apoJ expression by activated glia. LPS robustly increased NF-kappaB activation in mixed glial cultures. Two NF-kappaB inhibitors, aspirin (10 mm) and MG-132 (0.1 mum), blocked basal apoE and apoJ secretion as well as LPS-induced apoJ secretion. These data demonstrate that glial apoE and apoJ expression are independently regulated by LPS in microglia and astroglia, respectively, and that activated microglia are the predominant source of apoE in mixed glial cultures. The transcription factor NF-kappaB appears to be a critical mediator of LPS-stimulated apoJ expression from astroglia.