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（TNF）-Alpha是一种重要的免疫诱因促炎细胞因子。肺中TNF-Alpha的过表达会导致过滤的变化。 1.细胞因子，趋化因子和信号转导和交叉SP-C，用TNFR缺乏小鼠的TNF-Alpha转基因小鼠的tnf-Aloha透网式小鼠的分析表现出Th1-降低（kCCC）（MIP的上调），MALPHA转基因小鼠的分析和IIP（MIP）（MIP）（MIP（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIIP）（MIP）（MIP）（MIP）（MIP）（MIP）（MIP）（kC）趋化因子。对TNF-Alpha转基因小鼠中信号途径的研究表明，NF-κB在核，IK-B，A20和TNFR II中的增强。另一方面，观察到TNFRI和TRAF-2的降低，因此，我们将TNF-Alpha转基因小鼠与TNFRI或TNFRII缺陷小鼠穿越TNF-Alpha Transnic小鼠。此外，我们将测量未来的病理生理学。视黄酸对氯甲酸的影响已被称为肺肺气肿研究的注意力，因为据报道视黄酸会在大鼠的大鼠中重现弹性酶诱导的肺气肿。在这项研究中，我们研究了视黄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相反，维甲酸给药加剧了TNF-Alpha转基因小鼠的肺气肿样变化。黄牙酸治疗后，野生肺泡灌洗液中的角质形成细胞化学剂表现出TNF转基因小鼠的增加。这些数据表明，视黄酸可能会通过增加炎症而更严重的变化。