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Study of new therapy for COPD by regulation of inflammatory cytokines and oxidant stress

通过调节炎症细胞因子和氧化应激来治疗慢性阻塞性肺病的新疗法的研究

基本信息

批准号：
20790579
负责人：
KINOSHITA Takashi
金额：
$ 2.75万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2009
项目状态：
已结题

项目摘要

[Background]Caspase-1 is essential to maturity of IL-1 family cytokines IL-1beta, IL-18 and IL-33. We have recently reported that a significant correlation exists between serum levels of IL-18 and pulmonary function (%FEV_1) in COPD patients (Imaoka, ERJ 2009). Constitutive overproduction of mature IL-18 in the lungs of transgenic C57BL/6 mice resulted in severe emphysema lesions (Hoshino, AJRCCM 2007). We reported that redox-active protein thioredoxin 1 (TRX1) prevented the development and progression of elastase-induced emphysema in wild type C57BL/6 mice (Kinoshita, BBRC 2007). Both inflammatory cytokines and oxidative stress may be involved in the pathology of COPD. In this study, we investigated the roles of caspase-1 in elastase-induced COPD mouse model.[Material and methods]On day 0, C57BL/6 caspase-1 deficient (KO) mice and control wild type C57BL/6 mice and was anesthetized by intraperitoneal administration of thiopental (2.5 to 5 mg/mouse), and a microspray (MicroSprayer, Penn-Century, Inc., Philadelphia, PA) was inserted through its trachea. Fifty microliters of 0.9% physiological saline (vehicle) or 50 μL of purified porcine pancreatic elastase (PPE, 0.25 U) dissolved in saline was sprayed into the trachea. Mice were sacrificed on day 21. Lung tissues and bronchoalveolar lavage fluid (BALF) were histopathologically analyzed.[Result]A computerized color image analysis revealed that the mean alveolar chord length (30 +- 2.0μm), n = 5 for each group) was significantly reduced in elastase-treated caspase-1 KO mice, when compared with control wild type mice (39.9 +- 1.5 μm). In addition, inflammatory cells in BALF of(n = 10 for each group) was significantly prevented in elastase-treated caspase-1 KO mice.[Conclusion]Our results suggest that activation of caspase-1 may contribute to the pathogenesis of emphysematous changes and pulmonary inflammations in COPD patients.

[背景]Caspase-1是IL-1家族细胞因子IL-1β、IL-18和IL-33成熟所必需的。我们最近报道了COPD患者血清IL-18水平与肺功能(%FEV_1)之间存在显著的相关性(Imaoka，ERJ，2009)。转基因C57BL/6小鼠肺部结构性过度产生成熟IL-18导致了严重的肺气肿损害(Hoshino，AJRCCM 2007)。我们报道了氧化还原活性蛋白硫氧还蛋白1(TRX1)阻止弹性酶诱导的野生型C57BL/6小鼠肺气肿的发展和进展(Kinoshita，BBRC 2007)。炎症细胞因子和氧化应激都可能参与了COPD的病理过程。[材料与方法]第0天，C57BL/6 Caspase-1缺陷(KO)小鼠和对照野生型C57BL/6小鼠，经腹腔注射硫喷妥钠(2.5~5 mg/只)麻醉，气管内注入微喷雾剂(MicroSprayer，Penn-Century，Inc.，Philadelphia，PA)。气管内喷洒50微升0.9%生理盐水(Vev)或50μ的猪胰脏弹性蛋白酶(PPE0.25U)。第21天处死小鼠。[结果]计算机彩色图像分析显示，弹性酶处理组小鼠肺泡弦长(30±2.0μm，n=5)较对照野生型小鼠(39.9±1.5μm)明显缩短。此外，弹性酶处理的Caspase-1 KO小鼠(每组10只)的BALF中的炎性细胞明显受到抑制。[结论]caspase-1的激活可能参与了COPD患者肺气肿改变和肺部炎症的发病机制。

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）

Endogenous and Exogenous Thioredoxin 1 Prevents Goblet Cell Hyperplasia in a Chronic Antigen Exposure Asthma Model

DOI：
10.2332/allergolint.09-oa-0086
发表时间：
2009-09-01
期刊：
Allergology International
影响因子：
6.8
作者：
Imaoka, Haruki;Hoshino, Tomoaki;Aizawa, Hisamichi
通讯作者：
Aizawa, Hisamichi

Correlation of decreased survival and IL-18 in bone metastasis.

DOI：
10.2169/internalmedicine.48.1851
发表时间：
2009
期刊：
Internal medicine
影响因子：
1.2
作者：
M. Okamoto;K. Azuma;T. Hoshino;H. Imaoka;Jiro Ikeda;T. Kinoshita;S. Takamori;K. Ohshima;N. Edakuni;S. Kato;T. Iwanaga;H. Aizawa
通讯作者：
M. Okamoto;K. Azuma;T. Hoshino;H. Imaoka;Jiro Ikeda;T. Kinoshita;S. Takamori;K. Ohshima;N. Edakuni;S. Kato;T. Iwanaga;H. Aizawa

Interleukin-18 production and pulmonary function in COPD

COPD 患者中白细胞介素 18 的产生和肺功能

DOI：
发表时间：
2008
期刊：
Eur Respir J 31
影响因子：
0
作者：
lmaoka H;Okamoto M;他
通讯作者：
他

Clinical Characteristic of Lung Cancer Patients with Interstitial Pneumonia Treated with Chemotherapy or Radiotherapy

肺癌合并间质性肺炎化疗或放疗患者的临床特点

DOI：
发表时间：
2008
期刊：
影响因子：
0
作者：
Takashi Kinoshita;Koichi Azuma;Nobutaka Edakuni;Hideo Nakao;Masaki Okamoto;Jiro Ikeda;Tomoaki Hoshino;Tomoaki Iwanaga;Hisamichi Aizawa
通讯作者：
Hisamichi Aizawa

Expression of ERCC1 and class III beta-tubulin in non-small cell lung cancer patients treated with a combination of cisplatin/docetaxel and concurrent thoracic irradiation

顺铂/多西他赛联合胸部照射治疗非小细胞肺癌患者ERCC1和III类β微管蛋白的表达