Quercetin blocks airway epithelial cell chemokine expression
Quercetin blocks airway epithelial cell chemokine expression
复制标题
DOI：
10.1165/rcmb.2006-0149oc
复制
发表时间：
2006-11-01
影响因子：
6.4
通讯作者：
Hershenson, Marc B.
中科院分区：
文献类型：
--
作者：
Nanua, Suparna;Zick, Suzanna M.;Hershenson, Marc B.
槲皮素（3，3 '，4'，5，7-五羟基黄酮）是一种膳食类黄酮，是磷脂酰肌醇（PI）3-激酶的抑制剂和有效的抗氧化剂。我们推测槲皮素通过PI 3激酶依赖性机制阻断气道上皮细胞趋化因子的表达。用槲皮素和PI 3-激酶抑制剂LY 294002预处理分别降低了培养的人气道上皮细胞中TNF-α诱导的IL 8和单核细胞趋化蛋白（MCP）-1（也称为CCL 2）的表达。槲皮素还抑制TNF-α诱导的PI 3-激酶活性、Akt磷酸化、细胞内H2 O2产生、NF-κ B反式激活、IL-8启动子活性和稳态mRNA水平，这与槲皮素通过PI 3-激酶/Akt依赖性途径减弱NF-κ B反式激活来抑制趋化因子表达的观点一致。在转录抑制剂放线菌素D存在的情况下，槲皮素还减少TNF-α诱导的趋化因子分泌，同时诱导真核翻译起始因子（eIf）-2 α的磷酸化，表明槲皮素通过转录后和转录机制减弱趋化因子表达。最后，我们测试了槲皮素在蟑螂抗原致敏和攻击小鼠中的作用。这些小鼠表现出MCP-1依赖性气道高反应性和炎症。槲皮素显著降低肺MCP-1和乙酰甲胆碱反应性。我们的结论是槲皮素通过转录和转录后途径阻断气道细胞趋化因子的表达。
Quercetin (3,3',4',5,7-pentahydroxyflavone), a dietary flavonoid, is an inhibitor of phosphatidylinositol (PI) 3-kinase and potent antioxidant. We hypothesized that quercetin blocks airway epithelial cell chemokine expression via PI 3-kinase-dependent mechanisms. Pretreatment with quercetin and the PI 3-kinase inhibitor LY294002 each reduced TNF-alpha-induced IL8 and monocyte chemoattractant protein (MCP)-1 (also called CCL2) expression in cultured human airway epithelial cells. Quercetin also inhibited TNF-alpha-induced PI 3-kinase activity, Akt phosphorylation, intracellular H2O2 production, NF-kappa B transactivation, IL-8 promoter activity, and steady-state mRNA levels, consistent with the notion that quercetin inhibits chemokine expression by attenuating NF-kappa B transactivation via a PI 3-kinase/Akt-dependent pathway. Quercetin also reduced TNF-alpha-induced chemokine secretion in the presence of the transcriptional inhibitor actinomycin D, while inducing phosphorylation of eukaryotic translation initiation factor (eIf)-2 alpha, suggesting that quercetin attenuates chemokine expression by post-transcriptional as well as transcriptional mechanisms. Finally, we tested the effects of quercetin in cockroach antigen-sensitized and -challenged mice. These mice show MCP-1-dependent airways hyperresponsiveness and inflammation. Quercetin significantly reduced lung MCP-1 and methacholine responsiveness. We conclude that quercetin blocks airway cell chemokine expression via transcriptional and post-transcriptional pathways.