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Human amylin stimulates inflammatory cytokine secretion from human glioma cells
被引:17
|作者:
Gitter, BD
[1
]
Cox, LM
[1
]
Carlson, CD
[1
]
May, PC
[1
]
机构:
[1] Eli Lilly & Co, Lilly Res Labs, Neurosci Dis Res Div, Lilly Corp Ctr, Indianapolis, IN 46285 USA
关键词:
amylin;
Alzheimer's disease;
neuroinflammation;
D O I:
10.1159/000026432
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Chronic neurodegeneration in the brains of Alzheimer's disease (AD) patients may be mediated, at least in part, by the ability of amyloid beta (A beta) to exacerbate inflammatory pathways in a conformation-dependent manner. In this regard, we previously reported that the A beta-peptide-mediated potentiation of inflammatory cytokine secretion from interleukin-1 beta (IL-1 beta)-stimulated human astrocytoma cells was conformation dependent. Other amyloidogenic peptides, such as human amylin, which display similar conformation-dependent neurotoxic effects, may also elicit inflammatory cytokine secretion from glial cells. To test this hypothesis, we compared human and rat amylin for the effects on cytokine production in U-373 MG human astrocytoma cells. Human amylin alone stimulated U-373 MG cells to secrete IL-6 and IL-8 in a concentration-dependent manner with maximum effects seen at 10-25 mu M peptide. In addition, human amylin markedly potentiated IL-1 beta-stimulated cytokine production with a similar concentration dependence. In contrast, nonamyloidogenic rat amylin modestly stimulated cytokine secretion, either alone or combined with IL-1 beta. Aging human amylin resulted in diminished cytokine secretion, probably due to the formation of large, less active aggregates. In agreement with our previous studies using A beta, extracellular Ca2+ was necessary for human amylin stimulation of cytokine secretion. Our data suggest that amyloidogenic peptides promote cytokine secretion through similar beta-sheeted secondary-structure- and extracellular-Ca2+-dependent mechanism s. Copyright (C) 2000 S. Karger AG, Basel.
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页码:147 / 152
页数:6
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