Cornuside inhibits mast cell-mediated allergic response by downregulating MAPK and NF-κB signaling pathways
Cornuside inhibits mast cell-mediated allergic response by downregulating MAPK and NF-κB signaling pathways
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Cornuside 通过下调 MAPK 和 NF-kappa B 信号通路抑制肥大细胞介导的过敏反应
DOI：
10.1016/j.bbrc.2016.03.007
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发表时间：
2016-04-29
影响因子：
3.1
通讯作者：
Yan, Guanghai
中科院分区：
文献类型：
--
作者：
Li, Liangchang;Jin, Guangyu;Yan, Guanghai
目的：本研究旨在探讨山茱萸新苷对肥大细胞介导的过敏反应的影响及其可能的作用机制。
方法：为了在体内测试山茱萸新苷的抗过敏作用，在被动皮肤过敏反应模型大鼠中，通过局部注射抗二硝基苯免疫球蛋白E（IgE），随后静脉注射抗原进行攻击来诱导局部渗出。采用MTT法测定肥大细胞的活力。采用放射酶法测定大鼠腹腔肥大细胞中的组胺含量。为了研究山茱萸新苷影响组胺释放减少的机制，测量了钙摄取水平。为了检测山茱萸新苷是否影响促炎细胞因子的表达，进行了蛋白质印迹和酶联免疫吸附测定。
结果：口服山茱萸新苷抑制了大鼠的被动皮肤过敏反应。山茱萸新苷的存在减弱了IgE诱导的大鼠腹腔肥大细胞的组胺释放。山茱萸新苷对组胺释放的抑制作用是通过调节细胞内钙介导的。此外，山茱萸新苷降低了佛波醇12 - 肉豆蔻酸13 - 乙酸酯（PMA）和钙离子载体A23187刺激的人肥大细胞中促炎细胞因子如肿瘤坏死因子 - α和白细胞介素 - 6的产生和分泌。山茱萸新苷对促炎细胞因子的抑制作用依赖于核因子 - κB和p38丝裂原活化蛋白激酶。
结论：本研究提供的证据表明，山茱萸新苷通过阻断组胺释放和促炎细胞因子表达来抑制肥大细胞衍生的炎症性过敏反应。此外，山茱萸新苷在体内和体外的抗过敏作用表明该药物在炎症性过敏性疾病中可能具有治疗应用。（C）2016爱思唯尔公司。保留所有权利。
Aims: The present study is to investigate the effect of cornuside on mast cell-mediated allergic response, as well as its possible mechanisms of action.Methods: To test the anti-allergic effects of cornuside in vivo, local extravasation was induced by local injection of anti-dinitrophenyl immunoglobulin E (IgE) followed by intravenous antigenic challenge in passive cutaneous anaphylaxis model rats. Mast cell viability was determined using MTT assay. Histamine content from rat peritoneal mast cells was measured by the radioenzymatic method. To investigate the mechanisms by which cornuside affects the reduction of histamine release, the levels of calcium uptake were measured. To examine whether cornuside affects the expression of pro-inflammatory cytokines, Western blotting and ELISA were carried out.Results: Oral administration of cornuside inhibited passive cutaneous anaphylaxis in rats. Presence of cornuside attenuated IgE-induced histamine release from rat peritoneal mast cells. The inhibitory effect of cornuside on histamine release was mediated by the modulation of intracellular calcium. In addition, cornuside decreased phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated production and secretion of pro-inflammatory cytokines such as TNF-alpha: and IL-6 in human mast cells. The inhibitory effect of cornuside on pro-inflammatory cytokines was dependent on nuclear factor-kappa B and p38 mitogen-activated protein kinase.Conclusions: The present study provides evidence that cornuside inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. Furthermore, in vivo and in vitro anti-allergic effects of cornuside suggest a possible therapeutic application of this agent in inflammatory allergic diseases. (C) 2016 Elsevier Inc. All rights reserved.