期刊
ACS CHEMICAL NEUROSCIENCE
卷 11, 期 24, 页码 4262-4269出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.0c00537
关键词
Omarigliptin; blood-brain barrier; lipopolysaccharide; NF-kappa B
The blood-brain barrier (BBB) is an important barrier that separates brain tissue from peripheral blood. The permeability of the BBB can be destroyed by external harmful factors, such as lipopolysaccharide (LPS), which contributes to neuroinflammation and central nervous system diseases. The present study aims to investigate the protective effects of Omarigliptin against LPS-induced neuroinflammation and the underlying mechanism using a series of both in vivo and in vitro experiments. A neuroinflammation model was established by intraperitoneal injection of LPS into mice. We found that administration of Omarigliptin reduced LPS-induced inflammatory responses by inhibiting the expressions of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha). Importantly, we found that Omarigliptin protected the integrity of the BBB against LPS by increasing the expression of the tight junction proteins claudin-1 and claudin-5. Our results also demonstrate that Omarigliptin reduced LPS-induced increase in expressions of matrix matalloproteinases-2 ( P-2) and matrix matalloproteinases-9 (MMP-9) at both the mRNA and protein levels. Notably, Omarigliptin showed a powerful beneficial effect against LPS-induced cell damage in bEnd.3 brain endothelial cells by reducing the release of high mobility group box chromosomal protein 1 (HMGB-1). Consistently, Omarigliptin ameliorated LPS-induced exacerbation of endothelial permeability by increasing the expressions of claudin-1 and claudin-5 and reducing the expression of MMP-2 and MMP-9. Mechanistically, Omarigliptin inhibited the activation of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88/nuclear factor KB (TLR4/Myd88/NF-kappa B) signaling pathway. On the basis of these findings, we concluded that Omarigliptin might mitigate LPS-induced neuroinflammation and dysfunction of the integrity of the blood-brain barrier.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据