10-Hydroxydecanoic acid inhibits LPS-induced inflammation by targeting p53 in microglial cells
10-Hydroxydecanoic acid inhibits LPS-induced inflammation by targeting p53 in microglial cells
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10-羟基癸酸通过靶向小胶质细胞中的 p53 抑制 LPS 诱导的炎症
DOI：
10.1016/j.intimp.2020.106501
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发表时间：
2020
影响因子：
5.6
通讯作者：
Hu Fuliang
中科院分区：
文献类型：
--
作者：
You Mengmeng;Miao Zhuoning;Sienkiewicz Olimpia;Jiang Xiasen;Zhao Xin;Hu Fuliang
以小胶质细胞和星形胶质细胞活化为特征的神经炎症在许多神经系统疾病如阿尔茨海默病的发病机制中是重要的。非甾体类抗炎药（NSAIDs）是一类化学结构异质性药物，广泛应用于炎症的治疗。然而，由于这些药物对胃肠道和肝脏的副作用，其安全性日益受到关注。皇家浆（RJ）是一种潜在的功能性食品，由护士蜜蜂的下咽腺和下颌唾液腺分泌。在这项研究中，我们探讨了10-羟基癸酸（10-HDAA）的抗神经炎症作用，这是RJ中第二丰富但研究较少的脂肪酸。我们发现，10-HDAA降低脂多糖（LPS）诱导的诱导型一氧化氮合酶（iNOS）和一氧化氮（NO）的水平在小胶质细胞BV-2和N9细胞系的升高。与LPS组相比，10-HDAA/LPS处理的BV-2细胞具有更高水平的吞噬受体TREM 2。RNAseq转录组学结果显示BV-2细胞中LPS组和10-HDAA/LPS组之间的转录谱不同，并且10-HDAA预处理显著降低促炎介质的水平，这通过qRT-PCR分析进一步证实。此外，我们发现p53是10-HDAA的靶点。p53可能以两种方式介导10-HDAA的抗炎作用：首先通过直接灭活NLRP 3炎症通路，其次通过间接促进自噬。这些结果揭示了抑癌基因p53在抑制神经炎症中的新功能，为拓宽10-HDAA和RJ的应用范围提供了理论依据。
Neuroinflammation, characterized by the activation of microglia and astrocytes, is important in the pathogenesis of many neurological disorders, such as Alzheimer's disease. Nonsteroidal anti-inflammatory drugs (NSAIDs), a group of chemically heterogenous medications, are used widely in the treatment of inflammation. However, the safety of these drugs is a growing concern due to their side effects on the gastrointestinal tract and liver. Royal jelly (RJ) is a potential functional food produced by the hypopharynx and mandibular salivary glands of nurse bees. In this study, we explored the anti-neuroinflammatory effect of 10-hydroxydecanoic acid (10-HDAA), which is the second most abundant but less studied fatty acid in RJ. We showed that 10-HDAA decreased the lipopolysaccharide (LPS)-induced elevation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) levels in both microglial BV-2 and N9 cell lines. Compared to the LPS group, the 10-HDAA/LPS treated BV-2 cells had a higher level of the phagocytic receptor TREM2. RNAseq transcriptomic results showed a different transcriptional profile between the LPS group and the 10-HDAA/LPS group in BV-2 cells and the 10-HDAA pre-treatment significantly decreased levels o f pro-inflammatory mediators, which were further confirmed by qRT-PCR analysis. Moreover, we found that p53 was a target of 10-HDAA. p53 may mediate the anti-inflammation effect of 10-HDAA in two ways: first by directly deactivating the NLRP3 inflammatory pathway, second by indirectly promoting autophagy. Taken together, our results reveal a novel function of tumor suppressor p53 in the inhibition neuroinflammation and provide a theoretical basis for broadening the application range o f 10-HDAA and RJ.