Docosahexaenoic acid-containing choline phospholipid modulates LPS-induced neuroinflammation in vivo and in microglia in vitro.
Docosahexaenoic acid-containing choline phospholipid modulates LPS-induced neuroinflammation in vivo and in microglia in vitro.
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含有含二含胆碱磷脂的二十二碳六烯酸磷脂可在体外和小胶质细胞中调节LPS诱导的神经炎症。
DOI：
10.1186/s12974-017-0939-x
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发表时间：
2017-08-24
影响因子：
9.3
通讯作者：
Layé S
中科院分区：
文献类型：
--
作者：
Fourrier C;Remus-Borel J;Greenhalgh AD;Guichardant M;Bernoud-Hubac N;Lagarde M;Joffre C;Layé S
神经炎症过程被认为是一把双刃剑，对大脑既有保护作用，也有有害作用。小胶质细胞是大脑固有的免疫细胞，是神经炎症反应的关键组成部分。人们对开发针对小胶质细胞和控制神经炎症过程的药物越来越感兴趣。在这方面，二十二碳六烯酸（DHA），大脑的n-3多不饱和脂肪酸，是一个有希望调节促炎小胶质细胞和细胞因子产生的分子。一些研究报道，当DHA被酰化成磷脂时，DHA对大脑的生物利用度更高。在这项工作中，我们分析了dha -磷脂的抗炎活性，无论是在sn-1位置乙酰化（AceDoPC，一种稳定的形式，被认为具有优越的进入大脑的途径）还是在sn-1位置与棕榈酸酰化（PC-DHA）在体外和体内使用脂多糖（LPS）诱导的神经炎症模型。在体内，成年C57Bl6/J小鼠在LPS （i.p.）前24小时静脉注射AceDoPC或PC-DHA。在体外研究中，永生化的小鼠小胶质细胞BV-2与DHA形式和LPS共孵育。采用气相色谱法测定AceDoPC和PC-DHA对脑或BV-2 PUFA含量的影响。采用定量PCR或多重PCR检测lps诱导的促炎细胞因子白介素IL-1β、IL-6和肿瘤坏死因子(TNF) α的产生。体外FACS分析和western-blot检测IL-6受体和相关信号通路STAT3。在体内，单次注射AceDoPC或PC-DHA可减少lps诱导的小鼠海马中IL-6的产生。正如体外实验所显示的那样，这种效果可能与它们对小胶质细胞的直接作用有关。此外，AceDoPC或PC-DHA降低IL-6受体，而只有AceDoPC降低IL-6诱导的STAT3磷酸化。这些结果强调了给药dha -乙酰化成磷脂-通过对小胶质细胞的作用迅速调节lps诱导的神经炎症过程的效力。特别是，在小胶质细胞中，AceDoPC靶向IL-6的产生和信号传导。
Neuroinflammatory processes are considered a double-edged sword, having both protective and detrimental effects in the brain. Microglia, the brain’s resident innate immune cells, are a key component of neuroinflammatory response. There is a growing interest in developing drugs to target microglia and control neuroinflammatory processes. In this regard, docosahexaenoic acid (DHA), the brain’s n-3 polyunsaturated fatty acid, is a promising molecule to regulate pro-inflammatory microglia and cytokine production. Several works reported that the bioavailability of DHA to the brain is higher when DHA is acylated to phospholipid. In this work, we analyzed the anti-inflammatory activity of DHA-phospholipid, either acetylated at the sn-1 position (AceDoPC, a stable form thought to have superior access to the brain) or acylated with palmitic acid at the sn-1 position (PC-DHA) using a lipopolysaccharide (LPS)-induced neuroinflammation model both in vitro and in vivo. In vivo, adult C57Bl6/J mice were injected intravenously (i.v.) with either AceDoPC or PC-DHA 24 h prior to LPS (i.p.). For in vitro studies, immortalized murine microglia cells BV-2 were co-incubated with DHA forms and LPS. AceDoPC and PC-DHA effect on brain or BV-2 PUFA content was assessed by gas chromatography. LPS-induced pro-inflammatory cytokines interleukin IL-1β, IL-6, and tumor necrosis factor (TNF) α production were measured by quantitative PCR (qPCR) or multiplex. IL-6 receptors and associated signaling pathway STAT3 were assessed by FACS analysis and western-blot in vitro. In vivo, a single injection of AceDoPC or PC-DHA decreased LPS-induced IL-6 production in the hippocampus of mice. This effect could be linked to their direct effect on microglia, as revealed in vitro. In addition, AceDoPC or PC-DHA reduced IL-6 receptor while only AceDoPC decreased IL-6-induced STAT3 phosphorylation. These results highlight the potency of administered DHA—acetylated to phospholipids—to rapidly regulate LPS-induced neuroinflammatory processes through their effect on microglia. In particular, both IL-6 production and signaling are targeted by AceDoPC in microglia.
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DOI：
10.1016/j.plefa.2007.10.016
发表时间：
2007-11-01
影响因子：
3
作者：
Brenna, J. Thomas;Diau, Guan-Yeu
通讯作者：
Diau, Guan-Yeu
DOI：
10.1016/j.plefa.2014.01.005
发表时间：
2015-01-01
影响因子：
3
作者：
Lagarde, M.;Hachem, M.;Guichardant, M.
通讯作者：
Guichardant, M.
影响因子：
3.7
作者：
Dinel AL;André C;Aubert A;Ferreira G;Layé S;Castanon N
通讯作者：
Castanon N
影响因子：
4.7
作者：
Bernoud, N;Fenart, L;Lecerf, J
通讯作者：
Lecerf, J
影响因子：
4.7
作者：
De Smedt-Peyrusse, Veronique;Sargueil, Francoise;Laye, Sophie
通讯作者：
Laye, Sophie