Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia
Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia
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DOI：
10.1186/1742-2094-4-25
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发表时间：
2007-10-10
影响因子：
9.3
通讯作者：
Fiebich, Bernd L.
中科院分区：
文献类型：
--
作者：
Candelario-Jalil, Eduardo;de Oliveira, Antonio C. Pinheiro;Fiebich, Bernd L.
背景：神经炎症反应由不同的病理学触发，可以产生有益或有害的结果。小胶质细胞是参与神经炎症的主要细胞类型，释放多种介质，导致多种疾病（包括脑缺血和神经退行性疾病）中的神经元死亡。小胶质细胞激活的减弱已被证明可以提供针对不同类型脑损伤的保护作用。最近的证据表明白藜芦醇具有抗炎和有效的抗氧化特性。研究还表明，白藜芦醇是环氧合酶 (COX)-1 活性的有效抑制剂。先前的研究结果表明，该化合物能够减少体外和体内不同模型中的神经元损伤。本研究的目的是检查白藜芦醇是否能够减少脂多糖 (LPS) 激活的原代大鼠小胶质细胞产生前列腺素 E-2 (PGE(2)) 和 8-异前列腺素 F-2 α (8-iso-PGF(2 α))。方法：从新生大鼠大脑皮质中制备原代小胶质细胞培养物。在存在或不存在不同浓度的白藜芦醇（1-50μM）的情况下，用10ng/ml的LPS刺激小胶质细胞。孵育24小时后，收集培养基以使用酶免疫测定法测量PGE 2 和8-iso-PGF(2α)的产生。与 LPS 孵育 24 小时后，通过蛋白质印迹法研究 COX-1、COX-2 和微粒体前列腺素 E 合酶-1 ( mPGES-1) 的蛋白质水平。使用逆转录聚合酶链反应(RT-PCR)分析研究mPGES-1在mRNA水平的表达。结果：我们的结果表明，白藜芦醇可有效减少 LPS 诱导的 PGE(2) 合成和 8-iso-PGF(2 α) 的形成（自由基产生的量度）。有趣的是，白藜芦醇剂量依赖性地降低了关键酶 mPGES-1 的表达（mRNA 和蛋白质）。
Background: Neuroinflammatory responses are triggered by diverse ethiologies and can provide either beneficial or harmful results. Microglial cells are the major cell type involved in neuroinflammation, releasing several mediators, which contribute to the neuronal demise in several diseases including cerebral ischemia and neurodegenerative disorders. Attenuation of microglial activation has been shown to confer protection against different types of brain injury. Recent evidence suggests that resveratrol has anti- inflammatory and potent antioxidant properties. It has been also shown that resveratrol is a potent inhibitor of cyclooxygenase (COX)-1 activity. Previous findings have demonstrated that this compound is able to reduce neuronal injury in different models, both in vitro and in vivo. The aim of this study was to examine whether resveratrol is able to reduce prostaglandin E-2 (PGE(2)) and 8-iso-prostaglandin F-2 alpha (8-iso-PGF(2 alpha)) production by lipopolysaccharide (LPS)-activated primary rat microglia. Methods: Primary microglial cell cultures were prepared from cerebral cortices of neonatal rats. Microglial cells were stimulated with 10 ng/ml of LPS in the presence or absence of different concentrations of resveratrol (1-50 mu M). After 24 h incubation, culture media were collected to measure the production of PGE2 and 8- iso- PGF(2 alpha) using enzyme immunoassays. Protein levels of COX-1, COX-2 and microsomal prostaglandin E synthase-1 ( mPGES-1) were studied by Western blotting after 24 h of incubation with LPS. Expression of mPGES- 1 at the mRNA level was investigated using reverse transcription- polymerase chain reaction (RT-PCR) analysis. Results: Our results indicate that resveratrol potently reduced LPS- induced PGE(2) synthesis and the formation of 8-iso-PGF(2 alpha), a measure of free radical production. Interestingly, resveratrol dosedependently reduced the expression (mRNA and protein) of mPGES-1, which is a key enzyme.