Differential effects of pro- and anti-inflammatory cytokines alone or in combinations on the metabolic profile of astrocytes
Differential effects of pro- and anti-inflammatory cytokines alone or in combinations on the metabolic profile of astrocytes
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DOI：
10.1111/j.1471-4159.2010.07135.x
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发表时间：
2011-02-01
影响因子：
4.7
通讯作者：
Magistretti, Pierre J.
中科院分区：
文献类型：
--
作者：
Belanger, Mireille;Allaman, Igor;Magistretti, Pierre J.
我们以前曾报道过促炎细胞因子肿瘤坏死因子-α（TNF α）和白细胞介素-1 β（IL-1 β）诱导星形胶质细胞代谢谱的深刻改变。本研究旨在进一步表征细胞因子在星形胶质细胞中的作用，并确定是否也可以在神经元中观察到类似的作用。为此，将选定的促炎性（IL-6和干扰素-γ，以及上述TNF α和IL-1 β）和抗炎性细胞因子（IL-4、IL-10、转化生长因子-β 1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星形胶质细胞的葡萄糖利用，而抗炎细胞因子IL-4和IL-10降低星形胶质细胞的葡萄糖利用。相反，在神经元中未观察到显著变化。当在星形胶质细胞中共同应用成对的促炎细胞因子时，可以观察到几种添加剂或协同修饰。相反，IL-10部分减弱促炎细胞因子的作用。最后，在神经元-星形胶质细胞共培养物中，TNF α + IL-1 β和干扰素-γ诱导的星形胶质细胞代谢的改变调节了神经元对兴奋性毒性损伤的易感性。总之，这些结果表明，促炎细胞因子和抗炎细胞因子差异影响星形胶质细胞的代谢谱，这些变化对周围神经元有功能性影响。
P>We have previously reported that the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) 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-gamma, in addition to the above-mentioned TNF alpha and IL-1 beta) and anti-inflammatory cytokines (IL-4, IL-10, transforming growth factor-beta 1 and interferon-beta) 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 TNF alpha + IL-1 beta and interferon-gamma 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.