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 microg/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-kappa B (NF-kappa B) plays in glial activation, we assessed its possible role in mediating apoE and apoJ expression by activated glia. LPS robustly increased NF-kappa B activation in mixed glial cultures. Two NF-kappa B inhibitors, aspirin (10 mM) and MG-132 (0.1 microM), 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-kappa B appears to be a critical mediator of LPS-stimulated apoJ expression from astroglia.
Saura
Josep
J
Department of Pharmacology, Toxicology and Psychiatry, Indiana School of Medicine, Indianapolis, Indiana, USA.
Petegnief
Valerie
V
Wu
Xin
X
Liang
Yanbin
Y
Paul
Steven M
SM
D000818:Animals; D000831:Animals, Newborn; D001057:Apolipoproteins E / Q000096:biosynthesis* / Q000235:genetics; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D051152:Clusterin; D018920:Coculture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D001057:Apolipoproteins E; D051152:Clusterin; D016861:Cyclooxygenase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D006023:Glycoproteins; D008070:Lipopolysaccharides; D018832:Molecular Chaperones; D016328:NF-kappa B; D012333:RNA, Messenger; D009569:Nitric Oxide