Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Cytokine. 2019 Apr;116:48-60. doi: 10.1016/j.cyto.2019.01.001. Epub 2019 Jan 24.
Quercetin is a flavonoid polyphenolic compound present in fruits and vegetables that has proven anti-inflammatory activity. The goal of the present investigation was to investigate the effects of quercetin on tumor necrosis factor-α (TNF-α)-induced inflammatory responses via the expression of ICAM-1 and MMP-9 in human retinal pigment epithelial cells (ARPE-19 cells). Real-time PCR, gelatin zymography, and Western blot analysis showed that TNF-α induced the expression of ICAM-1 and MMP-9 protein and mRNA in a time-dependent manner. These effects were attenuated by pretreatment of ARPE-19 cells with quercetin. Quercetin inhibited the TNF-α-induced phosphorylation of PKCδ, JNK1/2, ERK1/2. Quercetin, rottlerin, SP600125 and U0126 attenuated TNF-α-stimulated c-Jun phosphorylation and AP-1-Luc activity. Pretreatment with quercetin, rottlerin, SP600125, or Bay 11-7082 attenuated TNF-α-induced NF-κB (p65) phosphorylation, translocation and RelA/p65-Luc activity. TNF-α significantly increased MMP-9 promoter activity and THP-1 cell adherence, and these effects were attenuated by pretreatment with quercetin, rottlerin, SP600125, U0126, tanshinone IIA or Bay 11-7082. These results suggest that quercetin attenuates TNF-α-induced ICAM-1 and MMP-9 expression in ARPE-19 cells via the MEK1/2-ERK1/2 and PKCδ-JNK1/2-c-Jun or NF-κB pathways.
槲皮素是一种存在于水果和蔬菜中的类黄酮多酚化合物，具有抗炎活性。本研究旨在探讨槲皮素通过调节人视网膜色素上皮细胞（ARPE-19 细胞）中 ICAM-1 和 MMP-9 的表达对 TNF-α诱导的炎症反应的影响。实时 PCR、明胶酶谱和 Western blot 分析显示，TNF-α呈时间依赖性诱导 ARPE-19 细胞中 ICAM-1 和 MMP-9 蛋白和 mRNA 的表达。槲皮素预处理可减弱 TNF-α诱导的这些作用。槲皮素抑制 TNF-α诱导的 PKCδ、JNK1/2 和 ERK1/2 的磷酸化。槲皮素、rottlerin、SP600125 和 U0126 减弱了 TNF-α刺激的 c-Jun 磷酸化和 AP-1-Luc 活性。槲皮素、rottlerin、SP600125 或 Bay 11-7082 预处理减弱了 TNF-α诱导的 NF-κB（p65）磷酸化、转位和 RelA/p65-Luc 活性。TNF-α显著增加 MMP-9 启动子活性和 THP-1 细胞黏附，槲皮素、rottlerin、SP600125、U0126、丹参酮 IIA 或 Bay 11-7082 预处理可减弱这些作用。这些结果表明，槲皮素通过 MEK1/2-ERK1/2 和 PKCδ-JNK1/2-c-Jun 或 NF-κB 途径减弱 TNF-α诱导的 ARPE-19 细胞中 ICAM-1 和 MMP-9 的表达。
