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学科主题临床医学
Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice
Li, Yu-Tao; He, Bei; Wang, Yu-Zhu; Wang, Jing
刊名RESPIRATORY RESEARCH
2009-08-25
DOI10.1186/1465-9921-10-79
10
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Respiratory System
研究领域[WOS]Respiratory System
关键词[WOS]OBSTRUCTIVE PULMONARY-DISEASE ; TRANSCRIPTION FACTOR ; AIRWAY INFLAMMATION ; GENE-EXPRESSION ; B ACTIVATION ; MATRIX-METALLOPROTEINASE ; DESTRUCTIVE INDEX ; AP-1 ACTIVITY ; KINASE-BETA ; EMPHYSEMA
英文摘要

To determine if nuclear factor-kappa B (NF-kappa B) activation may be a key factor in lung inflammation and respiratory dysfunction, we investigated whether NF-kappa B can be blocked by intratracheal administration of NF-kappa B decoy oligodeoxynucleotides (ODNs), and whether decoy ODN-mediated NF-kappa B inhibition can prevent smoke-induced lung inflammation, respiratory dysfunction, and improve pathological alteration in the small airways and lung parenchyma in the long-term smoke-induced mouse model system. We also detected changes in transcriptional factors. In vivo, the transfection efficiency of NF-kappa B decoy ODNs to alveolar macrophages in BALF was measured by fluorescein isothiocyanate (FITC)-labeled NF-kappa B decoy ODNs and flow cytometry post intratracheal ODN administration. Pulmonary function was measured by pressure sensors, and pathological changes were assessed using histology and the pathological Mias software. NF-kappa B and activator protein 1(AP-1) activity was detected by the electrophoretic motility shift assay (EMSA). Mouse cytokine and chemokine pulmonary expression profiles were investigated by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and lung tissue homogenates, respectively, after repeated exposure to cigarette smoke. After 24 h, the percentage of transfected alveolar macrophages was 30.00 +/- 3.30%. Analysis of respiratory function indicated that transfection of NF-kappa B decoy ODNs significantly impacted peak expiratory flow (PEF), and bronchoalveolar lavage cytology displayed evidence of decreased macrophage infiltration in airways compared to normal saline-treated or scramble NF-kappa B decoy ODNs smoke exposed mice. NF-kappa B decoy ODNs inhibited significantly level of macrophage inflammatory protein (MIP) 1 alpha and monocyte chemoattractant protein 1(MCP-1) in lung homogenates compared to normal saline-treated smoke exposed mice. In contrast, these NF-kappa B decoy ODNs-treated mice showed significant increase in the level of tumor necrosis factor-alpha (TNF-alpha) and pro-MMP-9(pro-matrix metalloproteinase-9) in mice BALF. Further measurement revealed administration of NF-kappa B decoy ODNs did not prevent pathological changes. These findings indicate that NF-kappa B activation play an important role on the recruitment of macrophages and pulmonary dysfunction in smoke-induced chronic lung inflammation, and with the exception of NF-kappa B pathway, there might be complex mechanism governing molecular dynamics of pro-inflammatory cytokines expression and structural changes in small airways and pulmonary parenchyma in vivo.

语种英语
WOS记录号WOS:000270143000001
资助机构National Natural Science Foundation Council (China)
引用统计
被引频次:19[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52545
专题北京大学第三临床医学院_呼吸科
作者单位Peking Univ, Hosp 3, Dept Resp Med, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Li, Yu-Tao,He, Bei,Wang, Yu-Zhu,et al. Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice[J]. RESPIRATORY RESEARCH,2009,10.
APA Li, Yu-Tao,He, Bei,Wang, Yu-Zhu,&Wang, Jing.(2009).Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice.RESPIRATORY RESEARCH,10.
MLA Li, Yu-Tao,et al."Effects of intratracheal administration of nuclear factor-kappaB decoy oligodeoxynucleotides on long-term cigarette smoke-induced lung inflammation and pathology in mice".RESPIRATORY RESEARCH 10(2009).
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