Analysis of IL-18-induced type-1 bronchial asthma

IL-18诱导的1型支气管哮喘分析

• 批准号: 16390291
• 负责人: YOSHIMOTO Tomohiro
• 金额: $ 9.02万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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/grant/KAKENHI-PROJECT-16390291/
• 关键词: bronchial asthma; IL-18; Th1 cells; airway hyperresponsiveness; IL-13; IFN-γ; infection; 気道過敏性

IL-18 was originally regarded to induce Th1-related cytokines. In general, factors favoring IFN-γ production are believed to abolish allergic diseases. Thus, we tested the role of IL-18 in regulation of bronchial asthma. To avoid background response of host-derived T cells, we administered memory type Th1 or Th2 cells into unsensitized mice and examined their relevant role in induction of bronchial asthma. Administration of Ag induced both airway inflammation and airway hyperresponsiveness (AHR) in mice receiving memory Th2 cells. In contrast, same treatment induced only airway inflammation but not AHR in mice receiving memory Th1 cells. However, these mice developed striking AHR when they were co-administered with IL-18. Furthermore, mice having received IFN-γ-expressing Th1 cells sorted from polarized Th1 cells developed severe airway inflammation and AHR following intranasal administration of Ag and IL-18. Thus, Th1 cells become very harmful cells when they are stimulated with Ag and IL-18. Newly polarized Th1 cells and IFN-γ-expressing Th1 cells, both of which express IL-18Rα chain strongly, produce IFN-γ, IL-9, IL-13, GM-CSF, TNF-α, RANTES and MIP-1α upon stimulation with Ag, IL-2 and IL-18 in vitro. Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.

IL-18最初被认为可以诱导th1相关的细胞因子。一般来说，促进IFN-γ产生的因素被认为可以消除过敏性疾病。因此，我们测试了IL-18在支气管哮喘调节中的作用。为了避免宿主源性T细胞的背景反应，我们将记忆型Th1或Th2细胞注入未致敏的小鼠，并研究了它们在诱导支气管哮喘中的相关作用。在接受记忆Th2细胞的小鼠中，Ag可诱导气道炎症和气道高反应性（AHR）。相比之下，同样的处理只会引起气道炎症，而不会引起记忆Th1细胞小鼠的AHR。然而，当这些小鼠与IL-18共同给药时，这些小鼠出现了惊人的AHR。此外，接受从极化Th1细胞中分选的表达IFN-γ的Th1细胞的小鼠在鼻内给予Ag和IL-18后出现严重的气道炎症和AHR。因此，当Th1细胞受到Ag和IL-18的刺激时，它们会变成非常有害的细胞。新极化Th1细胞和表达IFN-γ的Th1细胞均强烈表达IL-18Rα链，在体外经Ag、IL-2和IL-18刺激后产生IFN-γ、IL-9、IL-13、GM-CSF、TNF-α、RANTES和MIP-1α。因此，Ag和IL-18刺激记忆Th1细胞，在初始宿主中诱导严重的气道炎症和AHR。

项目成果

IL-18とアトピーモデル

IL-18 和特应性模型

• 发表时间: 2005
• 期刊: Molecular Medicine,免疫2006 42・臨時増刊号
• 作者: 善本知広;筒井ひろ子;中西憲司
• 通讯作者: 中西憲司

IL-18 together with anti-CD3 Ab induces human Th1 cells to induceTh1-, Th2-cytokines and IL-8.

IL-18 与抗 CD3 Ab 一起诱导人 Th1 细胞诱导 Th1-、Th2- 细胞因子和 IL-8。

• 发表时间: 2004
• 期刊: Int. Immunol. 16・12
• 作者: Hata H;Yoshimoto T;et al.
• 通讯作者: et al.

IL-18によるTh1型気管支喘息の誘導

IL-18诱导Th1型支气管哮喘

• 发表时间: 2004
• 期刊: アレルギー科 18・2
• 作者: Sawa;M.;Yamamoto;K.;Yokozawa;T.;Kiyoi;H.;Hishida;A.;Kajiguchi;T.;Seto;M.;Kohno;A.;Kitamura;K.;Itoh;Y.;Asou;N.;Hamajima;N.;Emi;N.;Naoe;T.;善本知広
• 通讯作者: 善本知広

Roles of IL-18 in basophils and mast cells.

• DOI: 10.2332/allergolint.55.105
• 发表时间: 2006
• 期刊: Allergology international : official journal of the Japanese Society of Allergology
• 作者: T. Yoshimoto;K. Nakanishi

IL-18とアレルギー性炎症

IL-18 与过敏性炎症

• 发表时间: 2004
• 期刊: 医学のあゆみ 211・6
• 作者: Kasugai;Y.;Tagawa;H.;Kameoka;Y.;Morishima;Y.;Nakamura;S.;Seto;M.;善本知広
• 通讯作者: 善本知広