L-阿拉伯糖通过减少 M1 巨噬细胞极化来减轻 LPS 诱导的肠道炎症和损伤。
L-arabinose Attenuates LPS-Induced Intestinal Inflammation and Injury through Reduced M1 Macrophage Polarization.
机构信息
State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
出版信息
J Nutr. 2023 Nov;153(11):3327-3340. doi: 10.1016/j.tjnut.2023.09.012. Epub 2023 Sep 15.
BACKGROUND
L-arabinose has anti-inflammatory and metabolism-promoting properties, and macrophages participate in the alleviation of inflammation; however, the mechanism by which they contribute to the anti-inflammatory effects of L-arabinose is unknown.
OBJECTIVES
To investigate the involvement of macrophages in the mitigation of L-arabinose in an intestinal inflammation model induced by lipopolysaccharide (LPS).
METHODS
Five-week-old male C57BL/6 mice were divided into 3 groups: a control and an LPS group that both received normal water supplementation, and an L-arabinose (ARA+LPS) group that received 5% L-arabinose supplementation. Mice in the LPS and ARA+LPS groups were intraperitoneally injected with LPS (10 mg/kg body weight), whereas the control group was intraperitoneally injected with the same volume of saline. Intestinal morphology, cytokines, tight junction proteins, macrophage phenotypes, and microbial communities were profiled at 6 h postinjection.
RESULTS
L-arabinose alleviated LPS-induced damage to intestinal morphology. L-arabinose down-regulated serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, and messenger RNA (mRNA) levels of TNF-α, IL-1β, interferon-γ (IFN-γ), and toll-like receptor-4 in jejunum and colon compared with those of the LPS group (P < 0.05). The mRNA and protein levels of occludin and claudin-1 were significantly increased by L-arabinose (P < 0.05). Interferon regulatory factor-5 (IRF-5) and signal transducer and activator of transcription-1 (STAT-1), key genes characterized by M1 macrophages, were elevated in the jejunum and colon of LPS mice (P < 0.05) but decreased in the ARA+LPS mice (P < 0.05). In vitro, L-arabinose decreased the proportion of M1 macrophages and inhibited mRNA levels of TNF-α, IL-1β, IL-6, IFN-γ, as well as IRF-5 and STAT-1 (P < 0.01). Moreover, L-arabinose restored the abundance of norank_f__Muribaculaceae, Faecalibaculum, Dubosiella, Prevotellaceae_UCG-001, and Paraasutterella compared with those of LPS (P < 0.05) and increased the concentration of short-chain fatty acids (P < 0.05).
CONCLUSION
The anti-inflammatory effects of L-arabinose are achieved by reducing M1 macrophage polarization, suggesting that L-arabinose could be a candidate functional food or nutritional strategy for intestinal inflammation and injury.
背景
L-阿拉伯糖具有抗炎和促进新陈代谢的特性，巨噬细胞参与了炎症的缓解；然而，它们在 L-阿拉伯糖抗炎作用中的贡献机制尚不清楚。
目的
研究巨噬细胞在脂多糖（LPS）诱导的肠道炎症模型中对 L-阿拉伯糖缓解作用的参与情况。
方法
将 5 周龄雄性 C57BL/6 小鼠分为 3 组：对照组和 LPS 组均给予普通水补充，L-阿拉伯糖（ARA+LPS）组给予 5% L-阿拉伯糖补充。LPS 和 ARA+LPS 组的小鼠腹膜内注射 LPS（10mg/kg 体重），而对照组腹膜内注射等量生理盐水。注射后 6 小时分析肠道形态、细胞因子、紧密连接蛋白、巨噬细胞表型和微生物群落。
结果
L-阿拉伯糖减轻了 LPS 诱导的肠道形态损伤。与 LPS 组相比，L-阿拉伯糖下调了血清肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β 和 IL-6 以及空肠和结肠中 TNF-α、IL-1β、干扰素-γ（IFN-γ）和 Toll 样受体-4 的信使 RNA（mRNA）水平（P<0.05）。L-阿拉伯糖显著增加了 occludin 和 claudin-1 的 mRNA 和蛋白水平（P<0.05）。干扰素调节因子-5（IRF-5）和信号转导和转录激活因子-1（STAT-1），即 M1 巨噬细胞的关键基因，在 LPS 小鼠的空肠和结肠中升高（P<0.05），但在 ARA+LPS 小鼠中降低（P<0.05）。体外，L-阿拉伯糖降低了 M1 巨噬细胞的比例，并抑制了 TNF-α、IL-1β、IL-6、IFN-γ、IRF-5 和 STAT-1 的 mRNA 水平（P<0.01）。此外，与 LPS 相比，L-阿拉伯糖恢复了 norank_f__Muribaculaceae、Faecalibaculum、Dubosiella、Prevotellaceae_UCG-001 和 Paraasutterella 的丰度（P<0.05），并增加了短链脂肪酸的浓度（P<0.05）。
结论
L-阿拉伯糖的抗炎作用是通过减少 M1 巨噬细胞极化来实现的，这表明 L-阿拉伯糖可能是一种用于肠道炎症和损伤的功能性食品或营养策略的候选物。
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