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A combination of LCPUFA ameliorates airway inflammation in asthmatic mice by promoting pro-resolving effects and reducing adverse effects of EPA

LCPUFA 组合通过促进促解作用和减少 EPA 的不良反应改善哮喘小鼠的气道炎症

  • 影响因子:6.86
  • DOI:10.1038/s41385-019-0245-2
  • 作者列表:"Fussbroich, D.","Colas, R. A.","Eickmeier, O.","Trischler, J.","Jerkic, S. P.","Zimmermann, K.","Göpel, A.","Schwenger, T.","Schaible, A.","Henrich, D.","Baer, P.","Zielen, S.","Dalli, J.","Beermann, C.","Schubert, R.
  • 发表时间:2020-01-06
Abstract

Lipid mediators derived from omega (n)-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA) play key roles in bronchoconstriction, airway inflammation, and resolution processes in asthma. This study compared the effects of dietary supplementation with either a combination of LCPUFAs or eicosapentaenoic acid (EPA) alone to investigate whether the combination has superior beneficial effects on the outcome of asthmatic mice. Mice were sensitized with house dust mite (HDM) extract, and subsequently supplemented with either a combination of LCPUFAs or EPA alone in a recall asthma model. After the final HDM and LCPUFA administration, airway hyperresponsiveness (AHR), bronchoalveolar lavages, and lung histochemistry were examined. Lipid mediator profiles were determined by liquid chromatography coupled with tandem mass spectrometry (LC–MS–MS). The LCPUFA combination reduced AHR, eosinophilic inflammation, and inflammatory cytokines (IL-5, IFN-γ, and IL-6) in asthmatic mice, whereas EPA enhanced inflammation. The combination of LCPUFAs was more potent in downregulating EPA-derived LTB_5 and LTC_5 and in supporting DHA-derived RvD1 and RvD4 (2.22-fold and 2.58-fold higher levels) than EPA alone. Ex vivo experiments showed that LTB_5 contributes to granulocytes’ migration and M1-polarization in monocytes. Consequently, the LCPUFA combination ameliorated airway inflammation by inhibiting adverse effects of EPA and promoting pro-resolving effects supporting the lipid mediator-dependent resolution program.

摘要

来源于 ω (n)-3 和 n-6 长链多不饱和脂肪酸 (LCPUFA) 的脂质介质在哮喘的支气管收缩、气道炎症和消退过程中起关键作用。本研究比较了膳食补充与 LCPUFAs 或二十碳五烯酸 (EPA) 单独组合的效果,以研究该组合是否对哮喘小鼠的结局具有优越的有益作用。小鼠用屋尘螨 (HDM) 提取物致敏,随后在回忆哮喘模型中单独补充 LCPUFAs 或 EPA 的组合。最后 HDM 和 LCPUFA 给药后,检测气道高反应性 (AHR) 、支气管肺泡灌洗和肺组织化学。通过液相色谱-串联质谱 (LC-MS) 测定脂质介质谱。LCPUFA 组合降低哮喘小鼠的 AHR 、嗜酸性粒细胞炎症和炎性细胞因子 (IL-5 、 IFN-γ 和 IL-6),而 EPA 增强炎症。LCPUFAs 的组合在下调 EPA 衍生的 LTB_5 和 LTC_5 以及支持 DHA 衍生的 RvD1 和 RvD4 (比 EPA 单独的水平高 2.22 倍和 2.58 倍) 方面更有效。体外实验表明,LTB_5 有助于粒细胞在单核细胞中的迁移和 M1-polarization。因此,LCPUFA 组合通过抑制 EPA 的不良反应和促进支持脂质介质依赖性解决方案的促解决作用来改善气道炎症。

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影响因子:3.94
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DOI:10.1016/j.taap.2019.114847
作者列表:["Bernstein DM","Toth B","Rogers RA","Kling DE","Kunzendorf P","Phillips JI","Ernst H"]

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DOI:10.1042/BST20191010
作者列表:["Zaragosi LE","Deprez M","Barbry P"]

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