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核桃提取物通过内吞 TLR4 抑制 LPS 诱导的 BV-2 小胶质细胞的激活:可能涉及磷脂酶 D2。

Walnut extract inhibits LPS-induced activation of BV-2 microglia via internalization of TLR4: possible involvement of phospholipase D2.

机构信息

USDA-ARS, Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.

出版信息

Inflammation. 2010 Oct;33(5):325-33. doi: 10.1007/s10753-010-9189-0.

DOI:10.1007/s10753-010-9189-0
PMID:20213499
Abstract

Walnuts are a rich source of essential fatty acids, including the polyunsaturated fatty acids alpha-linolenic acid and linoleic acid. Essential fatty acids have been shown to modulate a number of cellular processes in the brain, including the activation state of microglia. Microglial activation can result in the generation of cytotoxic intermediates and is associated with a variety of age-related and neurodegenerative conditions. In vitro, microglial activation can be induced with the bacterial cell wall component lipopolysaccharide (LPS). In the present study, we generated a methanolic extract of English walnuts (Juglans regia) and examined the effects of walnut extract exposure on LPS-induced activation in BV-2 microglial cells. When cells were treated with walnut extract prior to LPS stimulation, production of nitric oxide and expression of inducible nitric oxide synthase were attenuated. Walnut extract also induced a decrease in tumor necrosis-alpha (TNFalpha) production. We further found that walnut extract induced internalization of the LPS receptor, toll-like receptor 4, and that the anti-inflammatory effects of walnut were dependent on functional activation of phospholipase D2. These studies represent the first to describe the anti-inflammatory effects of walnuts in microglia, which could lead to nutritional interventions in the prevention and treatment of neurodegeneration.

摘要

核桃是必需脂肪酸的丰富来源,包括多不饱和脂肪酸α-亚麻酸和亚油酸。必需脂肪酸已被证明可以调节大脑中的许多细胞过程,包括小胶质细胞的激活状态。小胶质细胞的激活可导致细胞毒性中间体的产生,并与多种与年龄相关的和神经退行性疾病有关。在体外,可以用细菌细胞壁成分脂多糖 (LPS) 诱导小胶质细胞的激活。在本研究中,我们生成了一种英国胡桃(Juglans regia)的甲醇提取物,并研究了核桃提取物暴露对 LPS 诱导的 BV-2 小胶质细胞激活的影响。当细胞在 LPS 刺激前用核桃提取物处理时,一氧化氮的产生和诱导型一氧化氮合酶的表达被减弱。核桃提取物还诱导肿瘤坏死因子-α (TNFalpha) 的产生减少。我们进一步发现,核桃提取物诱导 LPS 受体,即 Toll 样受体 4 的内化,并且核桃的抗炎作用依赖于磷脂酶 D2 的功能激活。这些研究首次描述了核桃在小胶质细胞中的抗炎作用,这可能导致营养干预在预防和治疗神经退行性疾病中的应用。

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