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

肿瘤坏死因子(TNF)- α是一种重要的促炎细胞因子，具有免疫防御作用。tnf - α在肺中的过度表达可导致肺气肿变化。我们用这只老鼠做了下面描述的实验。细胞因子、趋化因子和信号转导分析，并交叉SP-C、TNF-aloha转基因小鼠与tnfr缺陷小鼠。tnf - α转基因小鼠表现出th1显性转移（ifn - γ和IL-12上调），CXC （KC）和CC （MIP）趋化因子均升高。对tnf - α转基因小鼠信号通路的研究表明，NF-κB在细胞核、IK-B、A20和TNFR II中表达增强。另一方面，观察到TNFRI和TRAF-2的减少，因此，我们将tnf - α转基因小鼠与TNFRI或TNFRII缺陷小鼠杂交。此外，我们将在未来测量病理生理学2。维甲酸对cop11的影响已引起肺气肿研究的关注，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。小鼠肺气肿模型再生。与弹性酶诱导的大鼠肺气肿相比，维甲酸加重了tnf - α转基因小鼠的肺气肿样变化。维甲酸处理后，支气管肺泡灌洗液中的角质细胞化学引诱剂显示TNF转基因小鼠增加。这些数据表明维甲酸可能通过增加炎症加重肺气肿变化。

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.