Cigarette smoking decreases global microRNA expression in human alveolar macrophages.
Cigarette smoking decreases global microRNA expression in human alveolar macrophages.
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DOI：
10.1371/journal.pone.0044066
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Monick MM
中科院分区：
文献类型：
--
作者：
Graff JW;Powers LS;Dickson AM;Kim J;Reisetter AC;Hassan IH;Kremens K;Gross TJ;Wilson ME;Monick MM
人肺泡巨噬细胞是先天免疫系统的重要组成部分。吸烟引起的肺泡巨噬细胞基因表达的变化与肺部感染抵抗力降低和肺气肿/慢性阻塞性肺疾病的发生有关。我们假设microRNAs(MiRNAs)可以部分控制在吸烟者肺泡巨噬细胞中发现的独特的信使RNA(MRNA)表达谱。巨噬细胞在体外用不同的刺激激活会导致不同范围的M1(炎症)和M2(抗炎)极化表型，这些表型被认为在不同的组织环境中模仿激活的巨噬细胞。微阵列信使核糖核酸数据显示，吸烟促进了“反向”的M1mRNA表达程序，其定义是M1诱导的转录本表达减少，M1抑制的转录本表达增加，而M2调节的转录本几乎没有变化。RT-PCR阵列检测到吸烟者肺泡巨噬细胞中许多miRNAs的表达发生了变化，并且全球miRNA丰度降低。对人类受试者的分层研究表明，miRNA丰度的全球下降幅度与吸烟史有关。我们发现，许多在吸烟者肺泡巨噬细胞中表达降低的miRNAs被预测为靶向在吸烟者肺泡巨噬细胞中上调的mRNAs。例如，miR-452被预测针对编码MMP12的转录本，MMP12是吸烟相关疾病的重要影响因素。在分化的单核细胞中，miR-452的实验性拮抗作用导致MMP12表达增加。这里描述的全面的mRNA和miRNA表达谱提供了对基因表达调控的洞察，这可能是吸烟对肺泡巨噬细胞产生不利影响的基础。
Human alveolar macrophages are critical components of the innate immune system. Cigarette smoking-induced changes in alveolar macrophage gene expression are linked to reduced resistance to pulmonary infections and to the development of emphysema/COPD. We hypothesized that microRNAs (miRNAs) could control, in part, the unique messenger RNA (mRNA) expression profiles found in alveolar macrophages of cigarette smokers. Activation of macrophages with different stimuli in vitro leads to a diverse range of M1 (inflammatory) and M2 (anti-inflammatory) polarized phenotypes that are thought to mimic activated macrophages in distinct tissue environments. Microarray mRNA data indicated that smoking promoted an “inverse” M1 mRNA expression program, defined by decreased expression of M1-induced transcripts and increased expression of M1-repressed transcripts with few changes in M2-regulated transcripts. RT-PCR arrays identified altered expression of many miRNAs in alveolar macrophages of smokers and a decrease in global miRNA abundance. Stratification of human subjects suggested that the magnitude of the global decrease in miRNA abundance was associated with smoking history. We found that many of the miRNAs with reduced expression in alveolar macrophages of smokers were predicted to target mRNAs upregulated in alveolar macrophages of smokers. For example, miR-452 is predicted to target the transcript encoding MMP12, an important effector of smoking-related diseases. Experimental antagonism of miR-452 in differentiated monocytic cells resulted in increased expression of MMP12. The comprehensive mRNA and miRNA expression profiles described here provide insight into gene expression regulation that may underlie the adverse effects cigarette smoking has on alveolar macrophages.
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DOI：
10.1056/nejmoa0904006
发表时间：
2009-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hunninghake GM;Cho MH;Tesfaigzi Y;Soto-Quiros ME;Avila L;Lasky-Su J;Stidley C;Melén E;Söderhäll C;Hallberg J;Kull I;Kere J;Svartengren M;Pershagen G;Wickman M;Lange C;Demeo DL;Hersh CP;Klanderman BJ;Raby BA;Sparrow D;Shapiro SD;Silverman EK;Litonjua AA;Weiss ST;Celedón JC
通讯作者：
Celedón JC
影响因子：
--
作者：
Hansdottir, Sif;Monick, Martha M.
通讯作者：
Monick, Martha M.
影响因子：
4.4
作者：
Chen, Haiyan;Cowan, Mark J.;Medvedev, Andrei E.
通讯作者：
Medvedev, Andrei E.
影响因子：
4.8
作者：
Izzotti, Alberto;Calin, George A.;De Flora, Silvio
通讯作者：
De Flora, Silvio
影响因子：
15.9
作者：
BITTERMAN, PB;RENNARD, SI;CRYSTAL, RG
通讯作者：
CRYSTAL, RG