The study on the regulation of allergic responses by opioid network in bronchial asthma

阿片网络调节支气管哮喘过敏反应的研究

• 批准号: 16616007
• 负责人: OHNO Isao
• 金额: $ 2.43万
• 依托单位: Tohoku Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16616007/
• 关键词: allergy; bronchial asthma; stress; opioid; μ-oploid receptor; Th2 cytokine; オピイド; オピオイド受容体; μ受容体

1.The effects of acute stress on allergic responses in asthma(1)Allergen-induced airway inflammation, in terms of the numbers of inflammatory cells in lung lavage fluids, in both restrain stressed-C57BL/6 and Balb/C female mice during allergen inhalation (acute stress) was significantly weaker than that in non restrain stressed-mice.(2)This effect of acute stress on the airway inflammation was observed also in μ opioid receptor-defficient C57BL/6 female mice.2.The effects of chronic stress on allergic responses in asthma(1)Following restrain stress during allergen inhalation, mice were further loaded with the stress once a day for 6 consecutive days (chronic stress). After the last stress, mice were inhaled with allergen, and lung lavage fluids were collected.(2)The numbers of inflammatory cells and the contents of Th2 cytokine including IL-4, IL-5 and IL-13 in lung lavage fluids in chronic stressed- C57BL/6 female mice were significantly higher than those in non chronic stressed-mice.(3)The increase of inflammatory cell numbers in chronic stressed-mice was abolished by the simultaneous administration of a μ opiois receptor antagonist β-FNA, with the stress.(4)In μ opioid receptor-defficient C57BL/6 female mice, the numbers of inflammatory cells and the contents of Th2 cytokine in lung lavage fluids were not significantly different between with and without chronic stress.These results suggest,that acute and chronic stress have opposite effects, the improvement and exacerbation, respectively, on allergen-induced airway inflammation.that the effect of chronic stress, but not acute stress, was mediated, at least in part, by μ opioid receptors,and that one of the mechanisms underlying the exacerbation by chronic stress is the shift of immune responses to Th2 through the activation of μ opioid receptors.We are attempting to investigate the role of μ opioid receptors on hypothalamus-pituitary-adrenal axis and on T lymphocytes in the immune deviation.

1.急性应激对哮喘变态反应的影响(1)变应原诱导的呼吸道炎症，以肺灌洗液中炎症细胞的数量为指标，在束缚应激组和BALB/C雌性小鼠吸入变应原时(急性应激)均明显弱于非束缚应激组。(2)急性应激对μ阿片受体缺陷的C57BL/6雌性小鼠的呼吸道炎症也有影响。2.慢性应激对哮喘过敏反应的影响(1)在过敏原吸入期间束缚应激后，再给小鼠施加应激，每天1次，连续6d(慢性应激)。(2)慢性应激-C57BL/6雌性小鼠肺灌洗液中炎症细胞数和Th2型细胞因子IL-4、IL-5和IL-13的含量显著高于非慢性应激小鼠。(3)μ阿片受体拮抗剂β-FNA与应激同时给予μ阿片受体拮抗剂C57BL/6雌性小鼠，可消除慢性应激小鼠肺灌洗液中炎症细胞数量的增加。慢性应激与非慢性应激肺灌洗液中炎症细胞数量和Th2型细胞因子含量无显著差异。提示急性应激和慢性应激对过敏原诱导的呼吸道炎症具有相反的作用，分别是改善和加重。慢性应激的作用，而不是急性应激，至少部分是通过μ阿片受体介导的。而慢性应激加重的机制之一是通过激活μ阿片受体改变对Th2型的免疫反应。我们试图探讨μ阿片受体在下丘脑-垂体-肾上腺轴和T淋巴细胞免疫偏离中的作用。

项目成果

Exacerbation of allergic airway inflammation by psychological stress

心理压力加剧过敏性气道炎症

• 发表时间: 2005
• 期刊: Respiration 24
• 作者: Kiyokawa;N.;Sekino;T.;Matsui;T.;Takenouchi;H.;Mimori;K.;Tang;W.R.;Matsui;J.;Taguchi;T.;Katagiri;Y.U.;Okita;H.;Matsuo;Y.;Karasuyama;H.;Fujimoto;J.;Okuyama K
• 通讯作者: Okuyama K

The role of eosinophilic inflammation in the pathogenesis of allergic diseases : Eosinophils as tissue-repair cells

嗜酸性粒细胞炎症在过敏性疾病发病机制中的作用：嗜酸性粒细胞作为组织修复细胞

• 发表时间: 2005
• 期刊: Allergol 20
• 作者: Nakayama;T.;桑原 尚夫;Ohno I
• 通讯作者: Ohno I

Cigliatzone inhibits the antigen-induced leukotrienes production independently of PPARγ in RBL-2H3 mast cells

Cigliatzone 抑制 RBL-2H3 肥大细胞中抗原诱导的白三烯产生，与 PPARγ 无关

• 发表时间: 2005
• 期刊: Eur. J. Pharmacol 10
• 作者: Katsumoto;M.;Okuyama K
• 通讯作者: Okuyama K

アレルギー疾患の病態形成における好酸球性炎症の意義 : 組織修復細胞としての好酸球

嗜酸性粒细胞炎症在过敏性疾病发病机制中的意义：嗜酸性粒细胞作为组织修复细胞

• 发表时间: 2005
• 期刊: アレルギー科 20
• 作者: Akiba;H.;K.Takeda;Y.Kojima;Y.Usui;N.Harada;T.Yamazaki;J.Ma;K.Tezuka;H.Yagita;K.Okumura.;Yuko Kikuchi;大野 勲
• 通讯作者: 大野 勲

アレルギー性気道炎症の性差における性ホルモン及びリンパ球の役割

性激素和淋巴细胞在过敏性气道炎症性别差异中的作用

• 发表时间: 2006
• 期刊: 東北薬科大学研究誌 52(発表予定)
• 作者: Haruki T;Sakura H;Iwamoto Y;小松 聡子
• 通讯作者: 小松 聡子