Zhu Yan, Chen Xiao, Liu Zhan, Peng Yu-Ping, Qiu Yi-Hua
School of Biological & Basic Medical Sciences, Soochow University, 199 Renai Road, Suzhou 215123, China.
Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong 226001, China.
Int J Mol Sci. 2015 Dec 28;17(1):25. doi: 10.3390/ijms17010025.
Interleukin (IL)-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS)-induced inflammatory Parkinson's disease (PD) cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM) cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL) 1 h prior to LPS (50 ng/mL) treatment. LPS induced dopaminergic and non-dopaminergic neuronal loss in VM cultures, VM neuron-enriched cultures, and neuron-microglia co-cultures, but not in neuron-astrocyte co-cultures. IL-10 reduced LPS-induced neuronal loss particularly in single VM neuron cultures. Pro-inflammatory mediators (TNF-α, IL-1β, inducible nitric oxide synthase and cyclooxygenase-2) were upregulated in both neuron-microglia and neuron-astrocyte co-cultures by LPS. In contrast, neurotrophic factors (brain-derived neurotrophic factor, insulin-like growth factor-1 or glial cell-derived neurotrophic factor) were downregulated in neuron-microglia co-cultures, but upregulated in neuron-astrocyte co-cultures by LPS. IL-10 reduced both the increase in production of the pro-inflammatory mediators and the decrease in production of the neurotrophic factors induced by LPS. These results suggest that astrocytes can balance LPS neurotoxicity by releasing more neurotrophic factors and that IL-10 exerts neuroprotective property by an extensive action including direct on neurons and indirect via inhibiting microglial activation.
白细胞介素（IL）-10是一种抗炎细胞因子，在大脑中表达，可抑制小胶质细胞的激活。在此，我们利用脂多糖（LPS）诱导的炎性帕金森病（PD）细胞模型，以确定小胶质细胞和星形胶质细胞是否是IL-10神经保护作用的必要靶点。制备了具有不同神经元、小胶质细胞和星形胶质细胞组成的原代腹侧中脑（VM）培养物。在LPS（50 ng/mL）处理前1小时，将细胞暴露于IL-10（15、50或150 ng/mL）。LPS在VM培养物、富含VM神经元的培养物和神经元-小胶质细胞共培养物中诱导多巴胺能和非多巴胺能神经元损失，但在神经元-星形胶质细胞共培养物中未诱导。IL-10减少了LPS诱导的神经元损失，特别是在单个VM神经元培养物中。促炎介质（肿瘤坏死因子-α、IL-1β、诱导型一氧化氮合酶和环氧化酶-2）在神经元-小胶质细胞和神经元-星形胶质细胞共培养物中均被LPS上调。相反，神经营养因子（脑源性神经营养因子、胰岛素样生长因子-1或胶质细胞源性神经营养因子）在神经元-小胶质细胞共培养物中被LPS下调，但在神经元-星形胶质细胞共培养物中被LPS上调。IL-10减少了LPS诱导的促炎介质产生的增加和神经营养因子产生的减少。这些结果表明，星形胶质细胞可通过释放更多神经营养因子来平衡LPS的神经毒性，并且IL-10通过广泛的作用发挥神经保护特性，包括直接作用于神经元和通过抑制小胶质细胞激活的间接作用。
