Prostaglandin E_2 inhibits airway inflammation

前列腺素 E_2 抑制气道炎症

• 批准号: 15591804
• 负责人: SHIMIZU Takeshi
• 金额: $ 2.05万
• 依托单位: Shiga University of Medical Science (2004)Mie University (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591804/
• 关键词: Prostaplandin E_2; LPS; Allergy; Nasal epithelium; mucus; Neutrophil; Eosinophil; IL-8

To examine the function of prostaglandin E_2 receptors on mucus hypersecretion in airway inflammation, we induced hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium by intranasal instillation of lipopolysaccharides(LPS), and by intranasal ovalbumin(OVA) instillation in OVA-sensitized rats. Subcutaneous injection of EP-4 agonist (ONO-AE1-329,1-100 μg/kg weight) dose-dependently inhibited LPS-induced mucus production and neutrophil infiltration. OVA-induced mucus production was also significantly inhibited by EP-4 agonist, however, eosinophil infiltration was not affected. Simultaneous injection of EP-4 agonist with intranasal OVA challenge (three instillations) significantly inhibited mucus production, but EP-4 injection with intraperitoneal OVA sensitization (four injections) did not. EP3 agonist (ONO-AE-248,100 μg/kg) also inhibited LPS-induced mucus production, whereas EP-1 agonist (ONO-DI-004) and EP-2 agonist (ONO-AE1-259-01) showed no effect.In vitro effects of EP agonists on airway epithelial cells were examined using NCI-H292 cells and human nasal epithelial cells cultured in air-liquid interface. Mucus secretion was evaluated by enzyme-linked immunosorbent assay using anti-mucin monoclonal antibodies (anti-MUC5AC and HCS18). Spontaneous mucus secretion and IL-8 secretion were not affected by EP agonists, however, LPS-induced mucus secretion was significantly inhibited by EP1,EP2,EP3,and EP4 agonists at 10^<-6>M, and LPS-induced IL-8 secretion was inhibited by EP3,and EP4 agonists. Spontaneous and LPS-induced IL-6 and GM-CSF secretion were not affected. These results indicate that prostaglandin E_2 inhibits mucus hypersecretion caused by LPS stimulation and allergic inflammation through the EP receptors/

为了研究前列腺素E_2受体对气道炎症粘液分泌过多的作用，我们通过鼻内滴注脂多糖（LPS）和鼻内滴注卵清蛋白（OVA）诱导大鼠鼻上皮杯状细胞肥大和化生变化。皮下注射EP-4激动剂（ONO-AE1-329,1-100 μg/kg体重）剂量依赖性地抑制LPS诱导的粘液产生和中性粒细胞浸润。 EP-4 激动剂也显着抑制 OVA 诱导的粘液产生，但嗜酸性粒细胞浸润不受影响。同时注射 EP-4 激动剂和鼻内 OVA 攻击（三次滴注）可显着抑制粘液产生，但注射 EP-4 和腹膜内 OVA 致敏（四次注射）则没有。 EP3 激动剂 (ONO-AE-248,100 μg/kg) 也抑制 LPS 诱导的粘液产生，而 EP-1 激动剂 (ONO-DI-004) 和 EP-2 激动剂 (ONO-AE1-259-01) 则没有效果。 使用 NCI-H292 细胞和培养的人鼻上皮细胞检查 EP 激动剂对气道上皮细胞的体外影响。 气液界面。使用抗粘蛋白单克隆抗体（抗MUC5AC和HCS18）通过酶联免疫吸附测定评估粘液分泌。自发性粘液分泌和IL-8分泌不受EP激动剂的影响，然而，LPS诱导的粘液分泌在10^-6M时被EP1、EP2、EP3和EP4激动剂显着抑制，并且LPS诱导的IL-8分泌被EP3和EP4激动剂抑制。自发的和 LPS 诱导的 IL-6 和 GM-CSF 分泌不受影响。这些结果表明，前列腺素E_2通过EP受体抑制LPS刺激和过敏性炎症引起的粘液分泌过多。