Mechanism of cigarette smoke-induced kinin B1 receptor expression in rat airways
Mechanism of cigarette smoke-induced kinin B1 receptor expression in rat airways
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DOI：
10.1016/j.peptides.2010.07.008
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发表时间：
2010-10-01
期刊：
影响因子：
3
通讯作者：
Morin, Andre
中科院分区：
文献类型：
--
作者：
Lin, James Chi-Jen;Talbot, Sebastien;Morin, Andre
肺部炎症是烟草烟雾相关性肺部疾病如慢性阻塞性肺疾病（COPD）的重要病理特征。已知激肽1型和2型受体（B-1 R、B-2 R）与肺和其它器官的炎症反应相关。在这项研究中，我们研究了香烟烟雾诱导的气道炎症是否可以上调B1 R和B2 R与IL-1 β和INF-α的相关性。用5 μ g/ml香烟烟雾的总颗粒物（TPM）处理24小时的大鼠肺切片显示，与媒介物处理（二甲基亚砜）相比，B1 R和IL-1 β的表达分别增强了5倍和30倍。然而，较高浓度的TPM未能诱导B1 R。未观察到B2 R或TNF-α基因诱导的显著增加。IL-1受体拮抗剂（IL-1 Ra，2ng/ml）可显著阻断TPM诱导的B1 R基因表达，而TNF-α抑制剂（500 μ M）可部分阻断TPM诱导的B1 R基因表达。Western印迹分析显示，在用5 μ g/m1 TPM处理24小时的大鼠肺切片中，B1 R的表达增加了2倍，并且这种蛋白质表达被用IL-1 Ra而不是用戊茶碱的共处理完全阻断。除了下呼吸道，大鼠气管亚慢性暴露于香烟全烟雾表现出11倍的B1 R基因诱导相比，只暴露于空气中。我们的研究结果表明，B1受体参与香烟烟雾诱导的气道炎症通过一种机制，这是由促炎细胞因子IL-1 β介导的。(C)2010年爱思唯尔公司All rights reserved.
Pulmonary inflammation is an important pathological feature of tobacco smoke related lung diseases such as chronic obstructive pulmonary disease (COPD). Kinin type 1 and type 2 receptors (B-1 R, B-2 R) are known to be associated with inflammatory responses of the lungs and other organs. In this study, we investigated whether cigarette smoke-induced airway inflammation could up-regulate B1R and B2R in correlation with IL-1 beta and INF-alpha. Rat lung slices treated with 5 mu g/ml total particulate matter (TPM) of cigarette smoke for 24 h showed an enhanced expression of B1R and IL-1 beta by 5-fold and 30-fold, respectively, in comparison to vehicle treatment (dimethyl sulfoxide). However, higher concentrations of TPM failed to induce B1R. No significant increase of B2R or TNF-alpha gene induction was observed. IL-1 receptor antagonist (IL-1Ra, 2 ng/ml) significantly blocked B1R gene induction by TPM, while 500 mu M pentoxifylline, TNF-alpha inhibitor, reduced it partially. Western blot analysis showed a 2-fold enhanced expression of B1R in rat lung slices treated with 5 mu g/m1 TPM for 24 h and such protein expression was totally blocked by a co-treatment with IL-1Ra but not with pentoxifylline. In addition to the lower airways, rat trachea subchronically exposed to cigarette whole smoke exhibited 11-fold B1R gene induction in comparison with those exposed only to air. Our results demonstrate the involvement of B1R in cigarette smoke-induced airway inflammation through a mechanism which is mediated by the pro-inflammatory cytokine IL-1 beta. (C) 2010 Elsevier Inc. All rights reserved.