期刊
EUROPEAN JOURNAL OF NUTRITION
卷 59, 期 7, 页码 2875-2892出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00394-019-02128-9
关键词
Trans-10-hydroxy-2-decenoic acid; Neuroinflammation; TNF-alpha/NF-kappa B axis; NLRP3 inflammasome; Autophagy; FOXO1
资金
- National Natural Science Foundation of China [31872431]
- earmarked fund for Modern Agro-industry Technology Research System from the Ministry of Agriculture of China [CARS-45]
Purpose Neuroinflammation is thought to be associated with the pathogenesis of a series of neurodegenerative diseases. We have previously reported that royal jelly (RJ) has an anti-inflammatory effect on microglial BV-2 cells. However, components contributing to the effect of RJ were largely unexplored. The aim of this study was to assess whethertrans-10-hydroxy-2-decenoic acid (10-HDA), the exclusive fatty acid in RJ, can alleviate neuroinflammation and to further explore the underlying mechanisms. Methods Immunohistochemistry staining, ELISA, qRT-PCR and Western blot were used to assess the effect of 10-HDA on LPS-induced neuroinflammation both in vivo and in vitro. To determine the extent of inflammatory changes after 10-HDA treatment, RNAseq transcriptomic analysis was conducted. Results 10-HDA pretreatment significantly reduced the production of pro-inflammatory mediators in LPS-treated C57BL/6J mice and microglial BV-2 cells. 10-HDA inhibited the activation of the TNF-alpha/NF-kappa B axis and NLRP3 inflammasome-IL-1 beta pathway, which may be the anti-neuroinflammatory mechanism of 10-HDA. We also demonstrated that 10-HDA triggered cell autophagy, as evidenced by elevated levels of microtubule-associated protein 1 light chain 3-II (LC3-II) and decreased expression of SQSTM1. More importantly, 10-HDA increased the transcriptional activity of FOXO1 by increasing FOXO1 nuclear localization. Inhibition of FOXO1 and autophagy using chemical inhibitors markedly blunted the effect of 10-HDA on the TNF-alpha pathway and NLRP3 inflammasome-IL-1 beta pathway, indicating that 10-HDA alleviates neuroinflammation in BV-2 cells by modulating FOXO1-mediated autophagy. Conclusions 10-HDA may be a promising agent for various neuroinflammation-associated diseases.
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