Quercetin as a Lyn kinase inhibitor inhibits IgE-mediated allergic conjunctivitis
Quercetin as a Lyn kinase inhibitor inhibits IgE-mediated allergic conjunctivitis
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槲皮素作为 Lyn 激酶抑制剂抑制 IgE 介导的过敏性结膜炎
DOI：
10.1016/j.fct.2019.110924
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发表时间：
2020-01-01
影响因子：
4.3
通讯作者：
He, Langchong
中科院分区：
文献类型：
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作者：
Ding, Yuanyuan;Li, Chaomei;He, Langchong
背景：由结膜反应性炎症引起的过敏性结膜炎是一种常见的眼表疾病。槲皮素以其抗过敏特性而闻名，但其对结膜炎的影响却鲜为人知。目的：研究槲皮素在结膜炎动物模型中的抗过敏作用，并探讨槲皮素在培养的人肥大细胞（MCs）中的作用机制。关键结果：槲皮素可抑制卵清蛋白（OVA）诱导的AC小鼠模型外周血IgE、HA、IL-4、tnf - α和p物质的表达。槲皮素还能减弱OVA诱导的AC模型结膜组织MC脱粒、嗜酸性粒细胞数量、P物质浓度和mRNA IL-4/ tnf - α表达。体外分析表明，槲皮素可减少DNP-HSA/IgE诱导的钙（Ca2+）内流，抑制LAD2细胞（人原代肥大细胞）的脱颗粒和趋化因子释放。槲皮素还能抑制DNP-HSA/IgE诱导的LAD2细胞中Lyn/PLC γ /IP3R-Ca2+激活、Lyn/ERK1/2信号传导和Lyn/ nf - κ B激活，这些都能促进炎症。单独添加槲皮素时，对PLC γ - 1的磷酸化和表达没有影响，但能有效抑制Lyn和磷酸化-Lyn。槲皮素（200 μ M）和Lyn抑制剂（巴非替尼，10 μ M）抑制Lyn激酶的活性，槲皮素可以通过Lyn激动剂（托咪酮，10 μ M）降低Lyn激酶的活性。这些数据可以初步确定槲皮素作为Lyn激酶抑制剂可以抑制过敏性结膜炎。结论和意义：本研究表明槲皮素可能通过抑制Lyn/PLC γ /IP3R-Ca2+、Lyn/ERK1/2和Lyn/ nf - κ B信号通路来治疗过敏性结膜炎。抑制Lyn可能代表了槲皮素在AC疾病模型中抑制炎症反应的主要机制。
Background: Allergic conjunctivitis (AC) resulting from conjunctival reactive inflammation is a common ocular surface disease. Quercetin is known for its anti-allergic properties but its effects on conjunctivitis are less well understood.Purpose: In this study, we evaluated the anti-allergic effects of quercetin in animal models of conjunctivitis, and explored its molecular mechanism(s) of action in cultured human mast cells (MCs).Key results: Quercetin inhibited the ovalbumin (OVA) induced expression of IgE, HA, IL-4, TNF-alpha and substance-P in the peripheral blood of AC mouse models. Quercetin also attenuated OVA induced MC degranulation, eosinophil number, substance P concentrations, and mRNA IL-4/TNF-alpha expression in the conjunctival tissue of AC models. In vitro analysis showed that quercetin reduced DNP-HSA/IgE induced calcium (Ca2+) influx, and suppressed degranulation and chemokine release in LAD2 cells (human primary mast cell). Quercetin also inhibited DNP-HSA/IgE induced Lyn/PLC gamma/IP3R-Ca2+ activation, Lyn/ERK1/2 signaling, and Lyn/NF-kappa B activation in LAD2 cells, all of which promote inflammation. When added alone, quercetin had no effect on PLC gamma 1 phosphorylation or expression, but potently inhibited Lyn and phosphorylation-Lyn. Quercetin (200 mu M) and Lyn inhibitors (Bafetinib, 10 mu M) inhibit the activity of Lyn kinase, and quercetin can reduce the activation of Lyn kinase by Lyn agonist (Tolimidone, 10 mu M). These data can be preliminarily determined that quercetin can inhibit allergic conjunctivitis as a Lyn kinase inhibitor.Conclusions and implications: This study illustrated the use of quercetin for the treatment of allergic conjunctivitis, which might act through its ability to inhibit Lyn/PLC gamma/IP3R-Ca2+, Lyn/ERK1/2, and Lyn/NF-kappa B signaling. The inhibition of Lyn likely represents a major mechanism by which quercetin dampens the inflammatory response in AC disease models.