Thymoquinone attenuates IgE-mediated allergic response via pi3k-Akt-NFκB pathway and upregulation of the Nrf2-HO1 axis
Thymoquinone attenuates IgE-mediated allergic response via pi3k-Akt-NFκB pathway and upregulation of the Nrf2-HO1 axis
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DOI：
10.1111/jfbc.13216
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发表时间：
2020-06-01
影响因子：
4
通讯作者：
Chandramoorthy, Harish C.
中科院分区：
文献类型：
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作者：
Dera, Ayed;Rajagopalan, Prasanna;Chandramoorthy, Harish C.
IgE依赖性反应介导大多数过敏性疾病。本研究探讨百里醌（Tq）对IgE介导的过敏反应在活化的肥大细胞，嗜碱性粒细胞和中性粒细胞的影响。Tq处理导致活化的RBL-2 H3细胞中TNF-α和IL-4水平的剂量依赖性降低。Tq抑制这些细胞的脱粒，IC 50值为56.37 μ M。此外，该化合物在肝素化人全血中抑制通过Fc ε RI受体诱导的嗜碱性粒细胞活化，IC 50值为45.76 μ M。同样，中性粒细胞迁移和弹性蛋白酶活性呈剂量依赖性降低。Tq降低了活化的RBL-2 H3细胞中Akt和NF κ B B的磷酸化水平，同时增加了核Nrf 2和HO-1抗氧化蛋白的表达。我们的研究结果表明，Tq具有可证明的活动在细胞模型的IgE介导的过敏reactions.Practical应用-目前的研究揭示了Tq的IgE为基础的反应在活化的肥大细胞，嗜碱性粒细胞和中性粒细胞的机制途径。这项临床前体外研究的结果可能会转化为Tq及其类似物在治疗过敏性炎症中更好的化疗应用。然而，建议对体内模型进行详细研究。
IgE-dependent reactions mediate the majority of allergic diseases. This study explores the effects of thymoquinone (Tq) on IgE-mediated allergic response in activated mast cells, basophils, and neutrophils. Tq treatment resulted in a dose-dependent decrease in levels of TNF-alpha and IL-4 in activated RBL-2H3 cells. Tq inhibited the degranulation of these cells with an IC50 value of 56.37 mu M. Moreover, the compound suppressed basophil activation induced through Fc epsilon RI receptors with an IC50 value of 45.76 mu M in heparinized human whole blood. Likewise, neutrophil migration and elastase activity were dose-dependently reduced. While Tq decreased the phosphorylation of Akt and NF kappa B in activated RBL-2H3 cells, it increased nuclear Nrf2 and HO-1 antioxidant proteins. Our results indicate that Tq possesses demonstrable activity in cellular models of IgE-mediated allergic reactions.Practical applications The current study sheds light on the mechanistic pathways of Tq on IgE-based response in activated mast cells, basophils, and neutrophils. The output of this preclinical in vitro study may be translated into better chemotherapeutic applications of Tq and its analogs in the treatment of allergic inflammation. However, a detailed investigation of in vivo models is recommended.