School of Food and Health, Beijing Technology and Business University, Beijing 100048, China.
Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100083, China.
Nutrients. 2024 Oct 22;16(21):3586. doi: 10.3390/nu16213586.
Hippocampal Neuroinflammation (HNF) is a critical driver of cognitive impairment. The lipopolysaccharide (LPS) accumulate amyloid beta (Aβ) and lead to HNF. The (BL) 99 have anti-inflammatory ability. However, whether BL99-derived microbiota-derived vesicles (MV) could alleviate LPS-induced HNF remains unclear.
To investigate, we used ultrafiltration with ultracentrifuge to extract BL99-derived-MV (BL99-MV). We used hippocampal neuronal HT22 cells (HT22) to establish the LPS-induced HNF model, and explored whether BL99-MV alleviate LPS-induced HNF.
The confocal microscopy showed that BL99-MV were taken up by HT22 and reduced the oxidative stress (ROS) level. The PCR showed that BL99-MV up-regulate IL-10 level, and down-regulate TNF-α, IL-1β, and IL-6. Transcriptomic analysis revealed 4127 differentially expressed genes, with 2549 genes upregulated and 1578 genes downregulated in the BL99-MV group compared to the LPS group. Compared to the LPS group, BL99-MV decreased FoxO6, IL-33, P53, and NFκB expression, but increased FoxO1 and Bcl2 expression. The WB showed that BL99-MV modulated NFκB, FoxO6, P53, Caspase9, and Caspase3 protein expression by reducing IL-33 expression in HT22. The findings demonstrated IL-33 as a regulator for FoxO6/P53 signaling.
Here, we hypothesized that BL99-MV alleviated LPS-induced HNF to promote HT22 survival and synaptic development by regulating FoxO6/P53 signaling by targeting IL-33.
海马神经炎症（HNF）是认知障碍的关键驱动因素。脂多糖（LPS）会积累淀粉样蛋白β（Aβ）并导致 HNF。BL 99 具有抗炎能力。然而，BL99 衍生的微生物衍生囊泡（MV）是否可以缓解 LPS 诱导的 HNF 尚不清楚。
为了进行研究，我们使用超滤和超速离心法提取 BL99 衍生的-MV（BL99-MV）。我们使用海马神经元 HT22 细胞（HT22）建立 LPS 诱导的 HNF 模型，并探讨 BL99-MV 是否可以缓解 LPS 诱导的 HNF。
共聚焦显微镜显示 BL99-MV 被 HT22 摄取并降低了氧化应激（ROS）水平。PCR 显示 BL99-MV 上调了 IL-10 水平，下调了 TNF-α、IL-1β 和 IL-6。转录组分析显示，与 LPS 组相比，BL99-MV 组有 4127 个差异表达基因，其中 2549 个基因上调，1578 个基因下调。与 LPS 组相比，BL99-MV 降低了 FoxO6、IL-33、P53 和 NFκB 的表达，但增加了 FoxO1 和 Bcl2 的表达。WB 显示 BL99-MV 通过降低 HT22 中的 IL-33 表达来调节 NFκB、FoxO6、P53、Caspase9 和 Caspase3 蛋白表达。研究结果表明，IL-33 作为 FoxO6/P53 信号的调节剂。
在这里，我们假设 BL99-MV 通过调节 FoxO6/P53 信号通路来减轻 LPS 诱导的 HNF，从而促进 HT22 的存活和突触发育，其作用靶点是 IL-33。
