Distinct Effects of Imperatorin on Allergic Rhinitis: Imperatorin Inhibits Caspase-1 Activity In Vivo and In Vitro
Distinct Effects of Imperatorin on Allergic Rhinitis: Imperatorin Inhibits Caspase-1 Activity In Vivo and In Vitro
复制标题
DOI：
10.1124/jpet.111.184275
复制
发表时间：
2011-10-01
影响因子：
3.5
通讯作者：
Jeong, Hyun-Ja
中科院分区：
文献类型：
--
作者：
Oh, Hyun-A;Kim, Hyung-Min;Jeong, Hyun-Ja
由于欧前胡素 (IPT)（呋喃香豆素类化合物）具有抗炎活性，因此我们推测 IPT 可能会调节过敏性鼻炎 (AR)。本研究的目的是分析 IPT 对 AR 的调节作用。在这里，我们展示了 IPT 在卵清蛋白 (OVA) 诱导的 AR 模型中的作用和机制。 OVA致敏小鼠在OVA攻击后的摩擦次数明显高于OVA未致敏小鼠。口服 IPT 可抑制摩擦次数的增加。 IPT 给药可降低 OVA 致敏小鼠中 IgE 和组胺水平的升高。给予IPT的AR小鼠的脾组织中干扰素-γ的水平增强，而白细胞介素(IL)-4的水平降低。 OVA致敏小鼠鼻粘膜中的IL-1β、巨噬细胞炎症蛋白2、细胞间粘附分子1和环氧合酶2的蛋白水平通过IPT施用而降低。在施用IPT的小鼠中，因OVA致敏而增加的嗜酸性粒细胞和肥大细胞浸润的数量也减少。此外，IPT 抑制同一鼻粘膜组织中的 caspase-1 活性。在活化的人肥大细胞中，受体相互作用蛋白 2 (RIP2)、I kappa B 激酶 (IKK)-beta、核因子 kappa B (NF-kappa B)/RelA 和 caspase-1 活化增加，但 RIP2、IKK-beta、NF-kappa B/RelA 和 caspase-1 活化的增加受到 IPT 治疗的抑制。此外，IPT 还能抑制 IgE 刺激的骨髓源性肥大细胞中的 caspase-1 活性和 IL-1 β 产生。我们可以得出结论，IPT 通过调节 AR 动物和体外模型中的 caspase-1 激活发挥显着作用。
Because imperatorin (IPT), the furanocoumarins exhibits anti-inflammatory activity, we reasoned that IPT might modulate the allergic rhinitis (AR). The aim of this study was to analyze the regulation of AR by IPT. Here, we show the effect and mechanism of IPT in an ovalbumin (OVA)-induced AR model. The number of rubs after the OVA challenge in the OVA-sensitized mice was significantly higher than that in the OVA-unsensitized mice. The increased number of rubs was inhibited by the oral administration of IPT. The increased levels of IgE and histamine in the OVA-sensitized mice were reduced by IPT administration. The levels of interferon-gamma were enhanced, whereas the levels of interleukin (IL)-4 were reduced on the spleen tissue of the IPT-administered AR mice. Protein levels of IL-1 beta, macrophage inflammatory protein-2, intercellular adhesion molecule-1, and cyclooxygenase-2 were reduced by IPT administration in the nasal mucosa of the OVA-sensitized mice. In the IPT-administered mice, the number of eosinophils and mast cells infiltration increased by OVA-sensitization were also decreased. In addition, IPT inhibited caspase-1 activity in the same nasal mucosa tissue. In activated human mast cells, the receptor-interacting protein 2 (RIP2), I kappa B kinase (IKK)-beta, nuclear factor-kappa B (NF-kappa B)/RelA, and caspase-1 activation were increased, but increased RIP2, IKK-beta, NF-kappa B/RelA, and caspase-1 activation were inhibited by the treatment of IPT. In addition, IPT inhibited caspase-1 activity and IL-1 beta production in IgE-stimulated bone marrow-derived mast cells. We can conclude that IPT exerts significant effects by regulating of caspase-1 activation in AR animal and in vitro models.