Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne (EPFL), Switzerland.
J Neurochem. 2011 Feb;116(4):564-76. doi: 10.1111/j.1471-4159.2010.07135.x. Epub 2011 Jan 19.
We have previously reported that the pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) induce profound modifications of the metabolic profile of astrocytes. The present study was undertaken to further characterize the effects of cytokines in astrocytes and to determine whether similar effects could also be observed in neurons. To do so, selected pro-inflammatory (IL-6 and interferon-γ, in addition to the above-mentioned TNFα and IL-1β) and anti-inflammatory cytokines (IL-4, IL-10, transforming growth factor-β1 and interferon-β) were applied to primary neuronal and astrocytic cultures, and key metabolic parameters were assessed. As a general pattern, we observed that pro-inflammatory cytokines increased glucose utilization in astrocytes while the anti-inflammatory cytokines IL-4 and IL-10 decreased astrocytic glucose utilization. In contrast, no significant change could be observed in neurons. When pairs of pro-inflammatory cytokines were co-applied in astrocytes, several additive or synergistic modifications could be observed. In contrast, IL-10 partially attenuated the effects of pro-inflammatory cytokines. Finally, the modifications of the astrocytic metabolism induced by TNFα + IL-1β and interferon-γ modulated neuronal susceptibility to an excitotoxic insult in neuron-astrocyte co-cultures. Together, these results suggest that pro- and anti-inflammatory cytokines differentially affect the metabolic profile of astrocytes, and that these changes have functional consequences for surrounding neurons.
我们之前曾报道过促炎细胞因子肿瘤坏死因子-α（TNFα）和白细胞介素-1β（IL-1β）可使星形胶质细胞的代谢谱发生深刻改变。本研究旨在进一步研究细胞因子对星形胶质细胞的影响，并确定类似的作用是否也能在神经元中观察到。为此，我们选择了一些促炎细胞因子（除上述 TNFα 和 IL-1β 之外，还有白细胞介素-6 和干扰素-γ）和抗炎细胞因子（白细胞介素-4、白细胞介素-10、转化生长因子-β1 和干扰素-β）应用于原代神经元和星形胶质细胞培养物，并评估了关键代谢参数。作为一般模式，我们观察到促炎细胞因子增加了星形胶质细胞的葡萄糖利用，而抗炎细胞因子 IL-4 和 IL-10 则降低了星形胶质细胞的葡萄糖利用。相比之下，神经元则没有明显的变化。当将促炎细胞因子成对应用于星形胶质细胞时，观察到了几种相加或协同的修饰。相反，IL-10 部分减弱了促炎细胞因子的作用。最后，TNFα+IL-1β 和干扰素-γ诱导的星形胶质细胞代谢改变调节了神经元在神经元-星形胶质细胞共培养物中对兴奋性损伤的敏感性。总之，这些结果表明，促炎和抗炎细胞因子可差异地影响星形胶质细胞的代谢谱，并且这些变化对周围神经元具有功能后果。
