Lipopolysaccharide (LPS)-induced dopamine cell loss in culture:: roles of tumor necrosis factor-α, interleukin-1β, and nitric oxide
Lipopolysaccharide (LPS)-induced dopamine cell loss in culture:: roles of tumor necrosis factor-α, interleukin-1β, and nitric oxide
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DOI：
10.1016/s0165-3806(01)00315-7
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发表时间：
2002-01-31
期刊：
影响因子：
--
通讯作者：
Carvey, PM
中科院分区：
文献类型：
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作者：
Gayle, DA;Ling, ZD;Carvey, PM
帕金森病（Parkinson's disease，PD）是一种以黑质多巴胺（dopamine，DA）神经元缺失为特征的神经退行性疾病。虽然负责这种细胞损失的确切机制尚不清楚。在本研究中，我们描述了促炎性细菌毒素脂多糖（LPS）对原代中脑培养物中酪氨酸羟化酶免疫反应（THir）细胞（用作DA神经元的指标）数量的影响。LPS（10-80 μ g/ml）选择性地减少THir细胞，并增加培养基中白细胞介素-10 1 β（IL-1 β）和肿瘤坏死因子-α（TNF-α）以及亚硝酸盐（一氧化氮（NO）产生的指标）的水平。暴露于LPS和IL-1 β或TNF-α的中和抗体的培养物在两种情况下均显示LPS诱导的THir细胞损失减弱至少50%。L-NIL抑制诱导型一氧化氮合酶（iNOS）不影响LPS毒性，但增加LPS诱导的TNF-α和IL-1 β水平。这些结果表明，导致细胞因子升高的神经炎症刺激可能以NO非依赖性方式诱导DA神经元细胞丢失，并促进PD发病。(C)2002 Elsevier Science B. V.保留所有权利。
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Although the exact mechanisms responsible for this cell loss are unclear. emerging evidence suggests the involvement of inflammatory events, In the present study, we characterized the effects of the proinflammatory bacteriotoxin lipopolysaccharide (LPS) on the number of tyrosine hydroxylase immunoreactive (THir) cells (used as an index for DA neurons) in primary mesencephalic cultures. LPS ( 10-80 mug/ml) selectively decreased THir cells and increased culture media levels of interleukin-10 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as well as nitrite (an index of nitric oxide (NO) production). Cultures exposed to both LPS and neutralizing antibodies to IL-1beta or TNF-alpha showed an attenuation of the LPS-induced THir cell loss by at least 50% in both cases. Inhibition of the inducible form of nitric oxide synthase (iNOS) by L-NIL did not affect LPS toxicity, but increased the LPS-induced levels of both TNF-alpha and IL-1beta, These findings suggest that neuroinflammatory stimuli which lead to elevations in cytokines may induce DA neuron cell loss in a NO-independent manner and contribute to PD pathogenesis. (C) 2002 Elsevier Science B.V. All rights reserved.