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Quercetin inhibits LPS-induced macrophage migration by suppressing the iNOS/FAK/paxillin pathway and modulating the cytoskeleton.
Cell Adhesion & Migration ( IF 3.3 ) Pub Date : 2018-08-01 , DOI: 10.1080/19336918.2018.1486142
Shuna Cui 1, 2, 3 , Qingqing Wu 1 , Juan Wang 1 , Min Li 1 , Jing Qian 1, 2 , Shihua Li 2
Affiliation  

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.

中文翻译:

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

天然黄酮类槲皮素具有抗氧化,抗炎和抗癌作用。我们调查了槲皮素对脂多糖(LPS)诱导的巨噬细胞迁移的影响。槲皮素可显着减弱RAW264.7细胞中LPS诱导的一氧化氮合酶(iNOS)衍生的一氧化氮(NO)的产生,而不会影响其生存能力。此外,槲皮素改变了细胞大小并诱导了伸长的形态,并扩大了液泡和浓缩的细胞核。槲皮素显着破坏F-肌动蛋白的细胞骨架结构。此外,槲皮素以剂量依赖的方式强烈抑制LPS诱导的巨噬细胞粘附和迁移。此外,槲皮素抑制LPS诱导的p-FAK,p-paxillin,FAK和paxillin的表达,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生成,破坏F-肌动蛋白细胞骨架和抑制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性疾病的治疗剂的潜力。
更新日期:2019-11-01
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