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槲皮素通过抑制 iNOS/FAK/paxillin 通路和调节细胞骨架来抑制 LPS 诱导的巨噬细胞迁移。

Quercetin inhibits LPS-induced macrophage migration by suppressing the iNOS/FAK/paxillin pathway and modulating the cytoskeleton.

机构信息

a Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases , Department of Integrated Chinese and Western Medicine, Medical College of Yangzhou University , Yangzhou , China.

b Department of Gynecology and Obstetrics , Affiliated Hospital of Yangzhou University , Yangzhou , China.

出版信息

Cell Adh Migr. 2019 Dec;13(1):1-12. doi: 10.1080/19336918.2018.1486142. Epub 2018 Aug 1.

DOI:10.1080/19336918.2018.1486142
PMID:29945484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6527387/
Abstract

The natural flavonoid quercetin has antioxidant, anti-inflammatory, and anticancer effects. We investigated the effect of quercetin on lipopolysaccharide (LPS)-induced macrophage migration. Quercetin significantly attenuated LPS-induced inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) production in RAW264.7 cells without affecting their viability. Additionally, quercetin altered the cell size and induced an elongated morphology and enlarged the vacuoles and concentrated nuclei. Quercetin significantly disrupted the F-actin cytoskeleton structure. Furthermore, quercetin strongly inhibited LPS-induced macrophage adhesion and migration in a dose-dependent manner. Moreover, quercetin inhibited the LPS-induced expression of p-FAK, p-paxillin, FAK, and paxillin as well as the cytoskeletal adapter proteins vinculin and Tensin-2. Therefore, quercetin suppresses LPS-induced migration by inhibiting NO production, disrupting the F-actin cytoskeleton, and suppressing the FAK-paxillin pathway. Quercetin may thus have potential as a therapeutic agent for chronic inflammatory diseases.

摘要

天然类黄酮槲皮素具有抗氧化、抗炎和抗癌作用。我们研究了槲皮素对脂多糖 (LPS) 诱导的巨噬细胞迁移的影响。槲皮素显著减弱了 LPS 诱导的 RAW264.7 细胞中诱导型一氧化氮合酶 (iNOS) 衍生的一氧化氮 (NO) 的产生，而不影响其活力。此外，槲皮素改变了细胞大小，诱导出细长的形态，并使空泡增大，核浓缩。槲皮素显著破坏了 F-肌动蛋白细胞骨架结构。此外，槲皮素强烈抑制 LPS 诱导的巨噬细胞黏附和迁移，呈剂量依赖性。此外，槲皮素抑制 LPS 诱导的 p-FAK、p-paxillin、FAK 和 paxillin 以及细胞骨架衔接蛋白 vinculin 和 Tensin-2 的表达。因此，槲皮素通过抑制 NO 产生、破坏 F-肌动蛋白细胞骨架以及抑制 FAK-paxillin 途径来抑制 LPS 诱导的迁移。槲皮素因此可能具有作为慢性炎症性疾病治疗剂的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/99e6871cbb75/kcam-13-01-1486142-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/88e0aac7a494/kcam-13-01-1486142-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/c92ccf99618f/kcam-13-01-1486142-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/864f35041f26/kcam-13-01-1486142-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/9090af857b26/kcam-13-01-1486142-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/71fe2ba19e91/kcam-13-01-1486142-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/2960db3468a2/kcam-13-01-1486142-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/e76365fd7c94/kcam-13-01-1486142-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/3d574d4f706a/kcam-13-01-1486142-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/99e6871cbb75/kcam-13-01-1486142-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/88e0aac7a494/kcam-13-01-1486142-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/c92ccf99618f/kcam-13-01-1486142-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/864f35041f26/kcam-13-01-1486142-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/9090af857b26/kcam-13-01-1486142-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/71fe2ba19e91/kcam-13-01-1486142-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/2960db3468a2/kcam-13-01-1486142-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/e76365fd7c94/kcam-13-01-1486142-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/3d574d4f706a/kcam-13-01-1486142-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64df/6527387/99e6871cbb75/kcam-13-01-1486142-g009.jpg

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