Beta-amyloid peptide secretion by a microglial cell line is induced by beta-amyloid-(25-35) and lipopolysaccharide.
beta-Amyloid protein (betaAP) deposition is a neuropathologic hallmark of Alzheimer's disease (AD). Yet, the source of cerebral betaAP in AD is controversial. We examined the production of betaAP by the BV-2 immortalized microglial cell line using a sensitive enzyme immunoassay. Constitutive production of betaAP was detected in conditioned media from unstimulated BV-2 cells. Further, production of betaAP was induced by treatment of cultures by lipopolysaccharide (LPS) or betaAP-(25-35) and was inhibited by the calpain protease inhibitor MDL 28170. Treatment of BV-2 cells with LPS or betaAP-(25-35) did not affect cell-associated beta-amyloid precursor protein levels. These findings suggest that microglia may be an important source of betaAP in AD, and that microglial production of betaAP may be augmented by proinflammatory stimuli or by betaAP itself.
Bitting
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Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
Naidu
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A
Cordell
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B
Murphy
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GM
D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000096:biosynthesis* / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002461:Cell Line, Transformed; D017077:Culture Media, Conditioned; D006801:Humans; D007124:Immunoenzyme Techniques; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009857:Oncogenes; D010446:Peptide Fragments / Q000494:pharmacology*; D012680:Sensitivity and Specificity
D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)