Predicted effects of observed changes in the mRNA and microRNA transcriptome of lung neutrophils during S. pneumoniae pneumonia in mice.

Predicted effects of observed changes in the mRNA and microRNA transcriptome of lung neutrophils during S. pneumoniae pneumonia in mice.
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DOI:
10.1038/s41598-017-11638-7
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发表时间:
2017-09-12
期刊:
影响因子:
4.6
通讯作者:
Doerschuk CM
Doerschuk CM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gomez JC;Dang H;Kanke M;Hagan RS;Mock JR;Kelada SNP;Sethupathy P;Doerschuk CM

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中性粒细胞在调节炎症反应中的复杂作用越来越受到重视。我们的研究分析了S. pneumoniae pneumoniae肺炎,并进行了深入的计算机模拟分析。肺内滴注PBS或S. pneumoniae,并鉴定差异表达(DE)的mRNA和miR。肺中性粒细胞从S. pneumoniae pneumoniae pneumonia中含有4127个DE mRNA,其中36%上调至少2倍。在肺炎期间,肺嗜中性粒细胞增加模式识别受体、炎性介质受体、转录因子(包括NF-κB和AP-1、Nrf 2靶标)、细胞因子、趋化因子和其他炎性介质的表达。有趣的是,中性粒细胞对I型干扰素有反应,而它们都产生并对II型干扰素有反应。在mRNA和蛋白质水平上验证了炎症和免疫应答调节剂的表达。在查询的约1100个miR中,31个miR增加,67个miR减少,来自S.肺炎潜在的DE miR-靶DE mRNA相互作用的网络分析揭示了候选的关键调控miR。因此,S.肺炎克雷伯氏菌调节肺中性粒细胞的mRNA和miR表达,增加其应答能力并促进宿主防御。
The complex role of neutrophils in modulating the inflammatory response is increasingly appreciated. Our studies profiled the expression of mRNAs and microRNAs (miRs) in lung neutrophils in mice during S. pneumoniae pneumonia and performed in depth in silico analyses. Lung neutrophils were isolated 24 hours after intratracheal instillation of PBS or S. pneumoniae, and differentially expressed (DE) mRNAs and miRs were identified. Lung neutrophils from mice with S. pneumoniae pneumonia contained 4127 DE mRNAs, 36% of which were upregulated at least 2-fold. During pneumonia, lung neutrophils increase expression of pattern recognition receptors, receptors for inflammatory mediators, transcription factors including NF-κB and AP-1, Nrf2 targets, cytokines, chemokines and other inflammatory mediators. Interestingly, neutrophils responded to Type I interferons, whereas they both produced and responded to Type II interferon. Expression of regulators of the inflammatory and immune response was verified at the mRNA and protein level. Of approximately 1100 miRs queried, 31 increased and 67 decreased more than 2-fold in neutrophils from S. pneumoniae pneumonia. Network analyses of potential DE miR-target DE mRNA interactions revealed candidate key regulatory miRs. Thus, S. pneumoniae modulates mRNA and miR expression by lung neutrophils, increasing their ability to respond and facilitating host defense.
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