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桔梗皂苷D通过激活LXRα-ABCA1信号通路抑制脂多糖刺激的原代大鼠小胶质细胞的炎症反应。

Platycodin D Inhibits Inflammatory Response in LPS-Stimulated Primary Rat Microglia Cells through Activating LXRα-ABCA1 Signaling Pathway.

作者信息

Fu Yunhe, Xin Zhuoyuan, Liu Bin, Wang Jiaxin, Wang Jingjing, Zhang Xu, Wang Yanan, Li Fan

机构信息

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, China.

Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, China.

出版信息

Front Immunol. 2018 Jan 9;8:1929. doi: 10.3389/fimmu.2017.01929. eCollection 2017.

Abstract

Platycodin D (PLD), an effective triterpenesaponin extracted from , has been known to have anti-inflammatory effect. In the present study, we investigate the anti-inflammatory effects of PLD on LPS-induced inflammation in primary rat microglia cells. The results showed that PLD significantly inhibited LPS-induced ROS, TNF-α, IL-6, and IL-1β production in primary rat microglia cells. PLD also inhibited LPS-induced NF-κB activation. Furthermore, our results showed that PLD prevented LPS-induced TLR4 translocation into lipid rafts disrupting the formation of lipid rafts by inducing cholesterol efflux. In addition, PLD could activate LXRα-ABCA1 signaling pathway which induces cholesterol efflux from cells. The inhibition of inflammatory cytokines by PLD could be reversed by SiRNA of LXRα. In conclusion, these results indicated that PLD prevented LPS-induced inflammation by activating LXRα-ABCA1 signaling pathway, which disrupted lipid rafts and prevented TLR4 translocation into lipid rafts, thereby inhibiting LPS-induced inflammatory response.

摘要

桔梗皂苷D(PLD)是从[具体来源未给出]中提取的一种有效的三萜皂苷,已知具有抗炎作用。在本研究中,我们研究了PLD对原代大鼠小胶质细胞中脂多糖(LPS)诱导的炎症的抗炎作用。结果表明,PLD显著抑制原代大鼠小胶质细胞中LPS诱导的活性氧(ROS)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)的产生。PLD还抑制LPS诱导的核因子-κB(NF-κB)激活。此外,我们的结果表明,PLD通过诱导胆固醇外流破坏脂筏的形成,阻止LPS诱导的Toll样受体4(TLR4)易位到脂筏中。此外,PLD可以激活肝X受体α(LXRα)-ATP结合盒转运蛋白A1(ABCA1)信号通路,该通路诱导胆固醇从细胞中外流。LXRα的小干扰RNA(SiRNA)可以逆转PLD对炎症细胞因子的抑制作用。总之,这些结果表明,PLD通过激活LXRα-ABCA1信号通路预防LPS诱导的炎症,该通路破坏脂筏并阻止TLR4易位到脂筏中,从而抑制LPS诱导的炎症反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437c/5767310/57bc0afca88d/fimmu-08-01929-g001.jpg

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