Regulation of microglial inflammatory response by sodium butyrate and short-chain fatty acids
Regulation of microglial inflammatory response by sodium butyrate and short-chain fatty acids
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DOI：
10.1038/sj.bjp.0705682
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发表时间：
2004-03-01
影响因子：
7.3
通讯作者：
Salminen, A
中科院分区：
文献类型：
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作者：
Huuskonen, J;Suuronen, T;Salminen, A
1最近的研究表明，丁酸钠和其他短链脂肪酸(SCFA)可以预防结肠疾病的炎症。我们的目的是阐明丁酸钠和单链脂肪酸对细胞培养中不同神经炎症模型的炎症反应是否有调节作用。2通过分泌一氧化氮(NO)和细胞因子IL-6和TNF-α来记录对内毒素诱导的小胶质细胞激活的炎症反应，并与核因子-kB复合体DNA结合活性的变化有关。3我们观察到丁酸钠对原代大鼠小胶质细胞以及在海马片培养和小胶质细胞、星形胶质细胞和小脑颗粒神经元的神经共培养中具有强烈的抗炎作用。4在小鼠N9小胶质细胞系中，丁酸钠和其他FASCs(丙酸、丁酸钠和其他FASCs)相反戊酸和己酸)可增强内毒素诱导的炎症反应。5内毒素暴露前预先给予丁酸盐的反应与同时给予丁酸盐和内毒素的反应相同或更强。6我们还观察到，在转化的N9细胞和海马片培养中，丁酸处理都下调了由脂多糖刺激诱导的NF-kB结合能力。7我们的结果表明，丁酸盐在原代脑源性小胶质细胞中具有抗炎作用，最近在结肠疾病中观察到，但在转化的、增殖的N9小胶质细胞中具有促炎作用，这可能与丁酸盐在肿瘤细胞中观察到的抗癌特性有关。
1 Recent studies have shown that sodium butyrate and other short-chain fatty acids (SCFAs) can prevent inflammation in colon diseases. Our aim was to elucidate whether sodium butyrate and SCFAs regulate the inflammatory responses in different neural inflammation models in cell cultures.2 Inflammatory responses to LPS-induced microglial activation were recorded by the secretion of nitric oxide (NO) and cytokines IL-6 and TNF-alpha and related to the changes in the DNA-binding activities of NF-kB complex.3 We observed that sodium butyrate is strongly anti-inflammatory against LPS-induced responses in rat primary microglia as well as in hippocampal slice cultures and in neural cocultures of microglial cells, astrocytes and cerebellar granule neurons.4 In murine N9 microglial cell line, instead, sodium butyrate and other SCFAs ( propionate, valerate and caproate) enhanced the LPS-induced inflammatory response.5 The pretreatment with butyrate before LPS exposure induced an equal or more enhanced response than simultaneous exposure with butyrate and LPS. This indicates that butyrate induces an adaptative response against microglial activation.6 We also observed that butyrate treatment both in transformed N9 cells and in hippocampal slice cultures downregulates the NF-kB-binding capacity induced by LPS stimulation.7 Our results show that butyrate is anti-inflammatory in primary, brain-derived microglial cells, as observed recently in colon diseases, but proinflammatory in transformed, proliferating N9 microglial cells, which may be related to the anticancer properties of butyrate observed in tumor cells.