Resveratrol differentially modulates inflammatory responses of microglia and astrocytes.
Resveratrol differentially modulates inflammatory responses of microglia and astrocytes.
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白藜芦醇差异调节小胶质细胞和星形胶质细胞的炎症反应
DOI：
10.1186/1742-2094-7-46
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发表时间：
2010-08-17
影响因子：
9.3
通讯作者：
Le Y
中科院分区：
文献类型：
--
作者：
Lu X;Ma L;Ruan L;Kong Y;Mou H;Zhang Z;Wang Z;Wang JM;Le Y
背景激活的神经胶质细胞介导的中枢神经系统炎症反应在宿主防御中发挥重要作用，但也参与神经退行性疾病的发生发展。白藜芦醇是一种天然多酚化合物，具有心脏保护、抗癌和抗炎等特性。研究白藜芦醇对炎性损伤小胶质细胞和星形胶质细胞的保护作用，探讨白藜芦醇对小胶质细胞和星形胶质细胞不同抑制作用的机制。采用聚合酶链式反应/实时定量聚合酶链式反应和酶联免疫吸附试验分别检测细胞表达和释放促炎细胞因子(肿瘤坏死因子-α、白介素1-β、白介素6、单核细胞趋化蛋白-1)和诱导型一氧化氮合酶/一氧化氮。结果脂多糖刺激小鼠小胶质细胞和星形胶质细胞表达肿瘤坏死因子-κ-α、IL-1β、IL-6、单核细胞趋化蛋白-1和诱导型一氧化氮合酶，其中MAP激酶、核因子-κB和AP-1参与其中。白藜芦醇抑制脂多糖诱导的小胶质细胞表达和释放肿瘤坏死因子α、白介素6、单核细胞趋化蛋白1和诱导型一氧化氮合酶/一氧化氮，抑制小胶质细胞表达白介素1β，但不抑制星形胶质细胞表达白介素1。白藜芦醇对脂多糖刺激的小胶质细胞和星形胶质细胞ERK1/2和p38的磷酸化无影响，但对脂多糖刺激的星形胶质细胞JNK的磷酸化有轻微的抑制作用。结论小鼠小胶质细胞和星形胶质细胞产生致炎细胞因子和NO的方式相似，但信号分子有所不同，白藜芦醇可能通过抑制不同的致炎细胞因子和关键信号分子对小胶质细胞和星形胶质细胞发挥抗炎作用。
BackgroundInflammatory responses in the CNS mediated by activated glial cells play an important role in host-defense but are also involved in the development of neurodegenerative diseases. Resveratrol is a natural polyphenolic compound that has cardioprotective, anticancer and anti-inflammatory properties. We investigated the capacity of resveratrol to protect microglia and astrocyte from inflammatory insults and explored mechanisms underlying different inhibitory effects of resveratrol on microglia and astrocytes.MethodsA murine microglia cell line (N9), primary microglia, or astrocytes were stimulated by LPS with or without different concentrations of resveratrol. The expression and release of proinflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1) and iNOS/NO by the cells were measured by PCR/real-time PCR and ELISA, respectively. The phosphorylation of the MAP kinase superfamily was analyzed by western blotting, and activation of NF-κB and AP-1 was measured by luciferase reporter assay and/or electrophoretic mobility shift assay.ResultsWe found that LPS stimulated the expression of TNF-α, IL-1β, IL-6, MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-κB and AP-1 were differentially involved. Resveratrol inhibited LPS-induced expression and release of TNF-α, IL-6, MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS-induced expression of IL-1β in microglia but not astrocytes. Resveratrol had no effect on LPS-stimulated phosphorylation of ERK1/2 and p38 in microglia and astrocytes, but slightly inhibited LPS-stimulated phosphorylation of JNK in astrocytes. Resveratrol inhibited LPS-induced NF-κB activation in both cell types, but inhibited AP-1 activation only in microglia.ConclusionThese results suggest that murine microglia and astrocytes produce proinflammatory cytokines and NO in response to LPS in a similar pattern with some differences in signaling molecules involved, and further suggest that resveratrol exerts anti-inflammatory effects in microglia and astrocytes by inhibiting different proinflammatory cytokines and key signaling molecules.
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影响因子：
5.3
作者：
McGuire, SO;Ling, ZD;Carvey, PM
通讯作者：
Carvey, PM
影响因子：
9.7
作者：
Hahm, ER;Cheon, G;Yang, CH
通讯作者：
Yang, CH
影响因子：
3.3
作者：
MATSUMOTO, Y;OHMORI, K;FUJIWARA, M
通讯作者：
FUJIWARA, M
DOI：
10.1016/s0165-3806(01)00315-7
发表时间：
2002-01-31
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Gayle, DA;Ling, ZD;Carvey, PM
通讯作者：
Carvey, PM
影响因子：
5.6
作者：
Bi, XL;Yang, JY;Wu, CF
通讯作者：
Wu, CF