Kim Sang-Hyun, Shin Tae-Yong
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Int Arch Allergy Immunol. 2006;139(2):87-95. doi: 10.1159/000090383. Epub 2005 Dec 16.
Stimulation of mast cells starts the process of degranulation resulting in release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of an aqueous extract of Dracocephalum argunense Fisch. (Labiatae) (DAAE) on immediate-type hypersensitivity and studied its possible mechanisms of action, focusing on histamine release and proinflammatory cytokine expression in mast cells.
An in vivo model of systemic and local allergic reaction was investigated. Compound 48/80- or IgE-induced histamine release from mast cells was measured. The expression of proinflammatory cytokines such as TNF-alpha and IL-6 was measured by RT-PCR and ELISA. The level of intracellular calcium was measured by spectrofluorometry. NF-kappaB activation was measured by Western blot, EMSA and luciferase assay.
DAAE inhibited systemic anaphylaxis, local allergic reactions, and serum histamine release in a dose-dependent manner in mice. DAAE dose-dependently reduced histamine release from mast cells activated by compound 48/80 or IgE. The inhibitory effect of DAAE on histamine release was mediated by the modulation of intracellular calcium. In addition, DAAE decreased TNF-alpha and IL-6 gene expression and production in human mast cells stimulated by phorbol-12-myristate-13-acetate (PMA) plus calcium ionophore A23187. The inhibitory effect of DAAE on the TNF-alpha and IL-6 expression was NF-kappaB dependent.
Our findings provide evidence that DAAE inhibits mast-cell-derived immediate-type hypersensitivity. Taken together, the anti-allergic effect of DAAE in vivo and in vitro suggests a possible clinical use of this agent in immediate-type hypersensitivity.
肥大细胞的刺激启动了脱颗粒过程，导致组胺和一系列炎性细胞因子等介质的释放。在本报告中，我们研究了阿尔泰青兰（唇形科）水提取物（DAAE）对速发型超敏反应的影响，并研究了其可能的作用机制，重点关注肥大细胞中组胺释放和促炎细胞因子表达。
研究了全身和局部过敏反应的体内模型。测量了化合物48/80或IgE诱导的肥大细胞组胺释放。通过RT-PCR和ELISA测量促炎细胞因子如TNF-α和IL-6的表达。通过荧光分光光度法测量细胞内钙水平。通过蛋白质免疫印迹、电泳迁移率变动分析和荧光素酶测定法测量NF-κB激活。
DAAE以剂量依赖性方式抑制小鼠全身过敏反应、局部过敏反应和血清组胺释放。DAAE剂量依赖性地减少了化合物48/80或IgE激活的肥大细胞的组胺释放。DAAE对组胺释放的抑制作用是通过调节细胞内钙介导的。此外，DAAE降低了佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）加钙离子载体A23187刺激的人肥大细胞中TNF-α和IL-6基因的表达和产生。DAAE对TNF-α和IL-6表达的抑制作用是NF-κB依赖性的。
我们的研究结果提供了证据表明DAAE抑制肥大细胞衍生的速发型超敏反应。综上所述，DAAE在体内和体外的抗过敏作用表明该药物在速发型超敏反应中可能具有临床应用价值。
