Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner.
Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner.
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DOI：
10.1186/1465-9921-11-134
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发表时间：
2010-10-04
影响因子：
5.8
通讯作者：
Brusselle GG
中科院分区：
文献类型：
--
作者：
Pauwels NS;Bracke KR;Maes T;Van Pottelberge GR;Garlanda C;Mantovani A;Joos GF;Brusselle GG
慢性阻塞性肺疾病（COPD）与气道、肺实质和肺血管的异常炎症反应和结构改变有关。由于正五聚蛋白-3（PTX 3）是炎症反应的调节剂，并且由内皮细胞和炎症细胞在诸如白细胞介素-1 β（IL-1β）的刺激下产生，因此我们假设PTX 3参与COPD发病机制。我们评估了香烟烟雾（CS）是否在COPD小鼠模型中触发体内肺和全身PTX 3表达。免疫组化染色观察到PTX 3在肺小静脉和静脉内皮细胞中表达，而在肺动脉、气道和肺实质中未见表达。此外，ELISA肺匀浆和IHC染色切片的半定量评分显示，在亚急性和慢性CS暴露后，PTX 3显著上调。有趣的是，在IL-1 RI KO小鼠中，在亚急性CS暴露后，PTX 3表达没有增强，这表明IL-1途径与CS诱导的血管PTX 3表达有关。急性CS暴露后，血清PTX 3水平迅速但短暂升高。为了阐明PTX 3在CS诱导的反应中的功能作用，我们检查了WT和Ptx 3 KO小鼠的肺部炎症、蛋白酶/抗蛋白酶平衡、肺气肿和体重变化。与WT小鼠相比，Ptx 3 KO小鼠中CS诱导的肺部炎症、支气管周围淋巴聚集、MMP-12/TIMP-1 mRNA比值增加、肺气肿和体重增加失败无显著差异。此外，Ptx 3缺陷并不影响CS诱导的VEGF-A和FGF-2（血管生成的重要调节因子）表达的改变。CS以IL-1依赖性方式增加肺PTX 3表达。然而，我们的研究结果表明，PTX 3是不是CS诱导的肺部炎症，肺气肿和体重变化的关键，或者它的作用可以通过其他介质与重叠的活动。
Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory responses and structural alterations of the airways, lung parenchyma and pulmonary vasculature. Since Pentraxin-3 (PTX3) is a tuner of inflammatory responses and is produced by endothelial and inflammatory cells upon stimuli such as interleukin-1β (IL-1β), we hypothesized that PTX3 is involved in COPD pathogenesis. We evaluated whether cigarette smoke (CS) triggers pulmonary and systemic PTX3 expression in vivo in a murine model of COPD. Using immunohistochemical (IHC) staining, we observed PTX3 expression in endothelial cells of lung venules and veins but not in lung arteries, airways and parenchyma. Moreover, ELISA on lung homogenates and semi-quantitative scoring of IHC-stained sections revealed a significant upregulation of PTX3 upon subacute and chronic CS exposure. Interestingly, PTX3 expression was not enhanced upon subacute CS exposure in IL-1RI KO mice, suggesting that the IL-1 pathway is implicated in CS-induced expression of vascular PTX3. Serum PTX3 levels increased rapidly but transiently after acute CS exposure. To elucidate the functional role of PTX3 in CS-induced responses, we examined pulmonary inflammation, protease/antiprotease balance, emphysema and body weight changes in WT and Ptx3 KO mice. CS-induced pulmonary inflammation, peribronchial lymphoid aggregates, increase in MMP-12/TIMP-1 mRNA ratio, emphysema and failure to gain weight were not significantly different in Ptx3 KO mice compared to WT mice. In addition, Ptx3 deficiency did not affect the CS-induced alterations in the pulmonary (mRNA and protein) expression of VEGF-A and FGF-2, which are crucial regulators of angiogenesis. CS increases pulmonary PTX3 expression in an IL-1 dependent manner. However, our results suggest that either PTX3 is not critical in CS-induced pulmonary inflammation, emphysema and body weight changes, or that its role can be fulfilled by other mediators with overlapping activities.
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影响因子：
5.8
作者：
Demedts, Ingel K.;Demoor, Tine;Bracke, Ken R.;Joos, Guy F.;Brusselle, Guy G.
通讯作者：
Brusselle, Guy G.
影响因子：
6.5
作者：
Abderrahim-Ferkoune, A;Bezy, O;Amri, EZ
通讯作者：
Amri, EZ
影响因子：
4.8
作者：
Camozzi, Maura;Rusnati, Marco;Presta, Marco
通讯作者：
Presta, Marco
影响因子：
24.3
作者：
Imai, K;Mercer, BA;D'Armiento, JM
通讯作者：
D'Armiento, JM
DOI：
10.1161/atvbaha.108.178947
发表时间：
2009-04
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Jenny NS;Arnold AM;Kuller LH;Tracy RP;Psaty BM
通讯作者：
Psaty BM