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The role of chronic inflammation on the pathogenesis for COPD, focusing on TNF-alpha.

慢性炎症在 COPD 发病机制中的作用，重点关注 TNF-α。

基本信息

批准号：
14570553
负责人：
FUJITA Masaki
金额：
$ 2.62万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570553/
关键词：
TNF-alpha Pulmonary emphysema Vitamin A Chemokine シゲナル伝達サイトカイン

项目摘要

Tumor necrosis factor (TNF)-alpha is an important proinflammatory cytokine for immune defence. Overexpression of TNF-alpha in the lung leads to emphysematous change. We used this mouse for performing the experiment described below.1.Analysis of cytokine, chemokine, and signal transduction and cross SP-C, TNF-aloha transgnenic mice with TNFR-deficient mice.TNF-alpha transgenic mice demonstrated Th1-dominant shift (upregulation of IFN-gamma and IL-12) and increase of both CXC (KC)and CC (MIP) chemokine. Investigation of signal pathway in TNF-alpha transgenic mice demonstrated the augmentation of NF-κB in nuclear, IK-B, A20, and TNFR II. On the other hand, decrease of TNFRI and TRAF-2 was observed, Hence, we are crossing TNF-alpha transgenic mice with either TNFRI or TNFRII deficient mice. Further, we will measure pathophysiology in future2.The effect of retinoic acid on COPDRetinoic acid has been called an attention concerning pulmonary emphysema research since retinoic acid has been reported to rescur elastase-induced emphysema in rats. In this study, we investigated whether or not retinoic acid also promote.regeneration in mouse emphysema model. In contrast to elastase-induced emphysema in rats, retinoic acid administration exacerbated emphysema-like changes in TNF-alpha transgenic mice. Keratinocyte chemoattractant in bronhoalveolar lavage fluids demonstrated increase in TNF transgenic mice after retinoic acid treatment. These data suggested that retinoic acid might worse emphysematous changes through augmentation of inflammation.

肿瘤坏死因子-α是一种重要的免疫防御促炎细胞因子。肺组织中肿瘤坏死因子-α的过度表达可导致肺气肿改变。1.细胞因子、趋化因子和信号转导的分析以及将SP-C、TNF-ALOHA转基因小鼠与TNFR缺陷小鼠杂交。结果表明，转基因小鼠表现出Th1-显性改变(干扰素-γ和IL-12上调)，CXC(KC)和CC(MIP)趋化因子增加。对肿瘤坏死因子-α转基因小鼠的信号通路的研究表明，在核、IK-B、A20和TNFRII中，NF-κB的表达增强。另一方面，观察到TRAF-2和TRAF-2的表达减少，因此，我们正在将肿瘤坏死因子-α转基因小鼠与TNFRI或TnFRII缺陷的小鼠杂交。维甲酸对COPD的影响一直是肺气肿研究的热点，因为有报道称维甲酸可以挽救弹性酶诱导的大鼠肺气肿。在这项研究中，我们研究了维甲酸是否也促进了小鼠肺气肿模型的再生。与弹性酶诱导的大鼠肺气肿不同，维甲酸的应用加剧了肿瘤坏死因子-α转基因小鼠的肺气肿样变。维甲酸治疗后，肿瘤坏死因子转基因小鼠的支气管肺泡灌洗液中的角质形成细胞趋化因子增加。这些数据表明，维甲酸可能通过增强炎症而加重肺气肿的改变。