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Study for roles of inflammatory cells and cytokines in asthma death, COPD and mouse pulmonary disease models

炎症细胞和细胞因子在哮喘死亡、慢性阻塞性肺病和小鼠肺部疾病模型中的作用研究

基本信息

批准号：
21590977
负责人：
HOSHINO Tomoaki
金额：
$ 2.91万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590977/
关键词：
喘息 COPD 動物モデル炎症細胞気道リモデリング炎症性サイトカイン IL-18

项目摘要

Background : Eosinophils, CD4+T cells, and Th2 cytokines are thought to contribute to the development of asthma. Recently, a paper reported that pro-inflammatory IL-18 gene polymorphism was significantly associated with the disease severity of bronchial asthma. However, the detail of airway inflammation process in the lungs of nonsmoker asthma death has not reported.Method : We obtained lung tissues from 12 nonsmokers who died of asthma at autopsy. They died from 1973 to 1998.Lung tissues were also obtained from 5 well-controlled mild asthma patients and 10 nonsmokers who underwent lung cancer extirpation. We examined pulmonary inflammatory cells, and also evaluated the expression of IL-18 and its receptor in the lungs.Result : The numbers of eosinophils and lymphocytes, but not basophils, nor macrophages were significantly and greatly increased in the lungs when compared with mild asthmatics and nonsmokers. Interestingly, neutrophils were not significantly different when comparing fatal and mild asthmas, but were significantly increased in the lungs of asthma deaths than seen in nonsmokers. CD8+T cells but not CD4+T cells were significantly and greatly increased in the lungs of fatal asthma patients when compared to mild asthmas and nonsmokers. IL-18 proteins were strongly expressed in the bronchoalveolar epithelial cells and pulmonary inflammatory cells in asthma deaths. Moreover, IL-18Rαproteins were enhanced in the pulmonary inflammatory cells, especially CD8+T cells in the lungs of asthma death.Conclusion : CD8+T cells, eosinophils and over-expressed IL-18 proteins in the lungs may play an important role in the pathogenesis of asthma death.

背景：嗜酸性粒细胞、CD 4 +T细胞和Th 2细胞因子被认为与哮喘的发生发展有关。最近有文献报道促炎因子IL-18基因多态性与支气管哮喘的病情严重程度显著相关。方法：我们从12例死于哮喘的非吸烟者尸检中获取肺组织，观察其病理变化。同时收集5例控制良好的轻度哮喘患者和10例非吸烟者肺癌切除术后的肺组织。结果：与轻度哮喘组和非吸烟者相比，哮喘组肺内嗜酸性粒细胞和淋巴细胞数量显著增加，嗜碱性粒细胞和巨噬细胞数量无显著性差异。有趣的是，当比较致命性和轻度哮喘时，中性粒细胞没有显著差异，但在哮喘死亡者的肺中比在非吸烟者中观察到的中性粒细胞显著增加。与轻度哮喘和非吸烟者相比，致命性哮喘患者的肺中CD 8 +T细胞显著增加，而CD 4 +T细胞则没有显著增加。IL-18蛋白在支气管肺泡上皮细胞和肺炎细胞中强烈表达。结论：CD 8 +T细胞、嗜酸性粒细胞和IL-18蛋白在哮喘死亡的发病机制中可能起重要作用。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Role of proinflammatory cytokines in respiratory diseases.

促炎细胞因子在呼吸系统疾病中的作用。

DOI：
发表时间：
2010
期刊：
影响因子：
0
作者：
奥山香織;和田佳奈;河野資;大河原雄一;田村弦;曽良一郎;高柳元明;大野勲;Hoshino T
通讯作者：
Hoshino T

Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis.

DOI：
10.1186/ar3295
发表时间：
2011-03-24
期刊：
Arthritis research & therapy
影响因子：
4.9
作者：
Takei S;Hoshino T;Matsunaga K;Sakazaki Y;Sawada M;Oda H;Takenaka S;Imaoka H;Kinoshita T;Honda S;Ida H;Fukuda TA;Aizawa H
通讯作者：
Aizawa H

Interleukin-18 and interleukin-18 receptor-alpha expression in allergic asthma

过敏性哮喘中白细胞介素 18 和白细胞介素 18 受体 α 的表达

DOI：
发表时间：
2011
期刊：
Eur Respir J
影响因子：
24.3
作者：
Imaoka H;Gauvreau GM;Watson RM;Smith SG;Dua B;Baatjes AJ;Howie K;Hoshino T;Killian KJ;Aizawa H;O' Byrne PM
通讯作者：
O' Byrne PM

Overexpression of chitinase 3-like 1/YKL-40 in lung-specific IL-18-transgenic mice, smokers and COPD.

DOI：
10.1371/journal.pone.0024177
发表时间：
2011
期刊：
PloS one
影响因子：
3.7
作者：
Sakazaki Y;Hoshino T;Takei S;Sawada M;Oda H;Takenaka S;Imaoka H;Matsunaga K;Ota T;Abe Y;Miki I;Fujimoto K;Kawayama T;Kato S;Aizawa H
通讯作者：
Aizawa H

Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein