Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke.
Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke.
复制标题
亚长期暴露于主流烟草烟雾的小鼠肺部白细胞介素 6/信号转导器和转录途径激活剂的诱导。
DOI：
10.1186/1755-8794-2-56
复制
发表时间：
2009-08-21
影响因子：
2.7
通讯作者：
Yauk, Carole L.
中科院分区：
文献类型：
--
作者：
Halappanavar, Sabina;Russell, Marsha;Stampfli, Martin R.;Williams, Andrew;Yauk, Carole L.
吸烟与肺癌和其他呼吸系统疾病有关。然而，对临床可检测症状出现之前的全局分子变化知之甚少。在这项研究中，研究了主流烟草烟雾（MTS）对小鼠肺全局转录的影响。雄性C57B1/CBA小鼠暴露于MTS，每天2支，每周5天，持续6或12周。小鼠立即或最后一支烟后6周被处死。使用高密度DNA微阵列来表征全肺中基因表达的变化。通过实时定量RT-PCR验证微阵列结果。采用酶联免疫吸附法和Western blotting对精选的一组基因进行进一步的蛋白质合成和功能分析。在全球范围内，79个基因在暴露于MTS后显著表达差异，这些基因与许多生物过程相关，包括异种代谢、氧化还原平衡、氧化应激和炎症。在最后一支香烟后6周，暴露于烟雾中的小鼠和采样的小鼠没有差异基因表达。此外，聚类分析表明，这些样本与各自的对照聚集在一起。我们观察到，在MTS暴露12周后，白细胞介素6 （IL-6）及其拮抗剂、细胞因子信号传导抑制因子（SOCS3） mRNA同时上调。ELISA和Western blotting分析显示，总肺组织提取物中总IL-6抗原水平及其下游靶标，包括磷酸化的信号换能器和转录激活因子3 （Stat3）、基底细胞淋巴瘤特大型（BCL-XL）和髓细胞白血病1 （MCL-1）蛋白水平同时升高。然而，与基因表达相反，在MTS暴露12周后，观察到总SOCS3蛋白的轻微下降。全球转录分析确定了一组对小鼠肺部MTS暴露有反应的基因。这些基因在戒烟后恢复到基础水平，为支持戒烟的益处提供了证据。对IL-6及其相关通路进行了详细分析。我们的研究结果进一步揭示了这些通路在MTS诱导的肺损伤和炎症中的作用。
Tobacco smoking is associated with lung cancer and other respiratory diseases. However, little is known about the global molecular changes that precede the appearance of clinically detectable symptoms. In this study, the effects of mainstream tobacco smoke (MTS) on global transcription in the mouse lung were investigated. Male C57B1/CBA mice were exposed to MTS from two cigarettes daily, 5 days/week for 6 or 12 weeks. Mice were sacrificed immediately, or 6 weeks following the last cigarette. High density DNA microarrays were used to characterize global gene expression changes in whole lung. Microarray results were validated by Quantitative real-time RT-PCR. Further analysis of protein synthesis and function was carried out for a select set of genes by ELISA and Western blotting. Globally, seventy nine genes were significantly differentially expressed following the exposure to MTS. These genes were associated with a number of biological processes including xenobiotic metabolism, redox balance, oxidative stress and inflammation. There was no differential gene expression in mice exposed to smoke and sampled 6 weeks following the last cigarette. Moreover, cluster analysis demonstrated that these samples clustered alongside their respective controls. We observed simultaneous up-regulation of interleukin 6 (IL-6) and its antagonist, suppressor of cytokine signalling (SOCS3) mRNA following 12 weeks of MTS exposure. Analysis by ELISA and Western blotting revealed a concomitant increase in total IL-6 antigen levels and its downstream targets, including phosphorylated signal transducer and activator of transcription 3 (Stat3), basal cell-lymphoma extra large (BCL-XL) and myeloid cell leukemia 1 (MCL-1) protein, in total lung tissue extracts. However, in contrast to gene expression, a subtle decrease in total SOCS3 protein was observed after 12 weeks of MTS exposure. Global transcriptional analysis identified a set of genes responding to MTS exposure in mouse lung. These genes returned to basal levels following smoking cessation, providing evidence to support the benefits of smoking cessation. Detailed analyses were undertaken for IL-6 and its associated pathways. Our results provide further insight into the role of these pathways in lung injury and inflammation induced by MTS.
登录
查看更多内容
影响因子：
5.8
作者：
Brandsma, Corry-Anke;Hylkema, Machteld N.;Kerstjens, Huib A. M.
通讯作者：
Kerstjens, Huib A. M.
DOI：
10.1164/ajrccm.156.1.9612018
发表时间：
1997-07-01
影响因子：
24.7
作者：
Finlay, GA;ODriscoll, LR;OConnor, CM
通讯作者：
OConnor, CM
影响因子：
4.7
作者：
Gebel, S;Gerstmayer, B;Müller, T
通讯作者：
Müller, T
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1016/j.bbrc.2005.03.099
发表时间：
2005-05-20
影响因子：
3.1
作者：
Dong, HY;Wade, M;Yauk, C
通讯作者：
Yauk, C