The nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide dampens lipopolysaccharide-induced transcriptomic changes in macrophages.
The nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide dampens lipopolysaccharide-induced transcriptomic changes in macrophages.
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DOI：
10.1007/s00011-018-1141-z
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Ramirez DC
中科院分区：
文献类型：
--
作者：
Muñoz MD;Della Vedova MC;Bushel PR;Ganini da Silva D;Mason RP;Zhai Z;Gomez Mejiba SE;Ramirez DC
巨噬细胞的m1样炎症表型在慢性炎症性疾病的组织损伤中起关键作用。先前，我们发现硝基自旋诱捕剂5,5-二甲基-1-吡咯啉n -氧化物（DMPO）抑制脂多糖（LPS）引发的RAW264.7细胞炎症启动。在此，我们测试了DMPO本身是否可以诱导巨噬细胞转录组的变化，并且这些作用可能阻止lps诱导的巨噬细胞活化。为了验证我们的假设，我们对RAW264.7细胞进行了转录组学和生物信息学分析，这些细胞在LPS和DMPO存在或不存在的情况下孵育。功能数据分析显示，DMPO与对照组有79个差异表达基因（DEGs）。我们使用DAVID数据库识别富集的基因本体术语，并使用Ingenuity Pathway Analysis进行功能分析。我们的数据显示，DMPO与对照比较deg与下调免疫系统过程有关。功能分析表明，干扰素反应因子7和toll样受体与观察到的DMPO转录组效应相关（预测抑制）。在RAW 264.7中，DMPO+LPS与LPS DEGs的功能数据分析与DMPO抑制LPS诱导的炎症转录组谱一致。这些变化通过纳米管柱技术得到了证实。综合我们的数据，令人惊讶的是，表明DMPO本身影响与免疫系统调节相关的基因表达，并且DMPO抑制lps触发的炎症转录组谱。我们的数据为进一步研究DMPO作为设计新型机制抗炎药的结构平台的可能性提供了关键数据。
M1-like inflammatory phenotype of macrophages plays a critical role in tissue damage in chronic inflammatory diseases. Previously, we found that the nitrone spin trap 5,5-dimethyl-1-pirroline N-oxide (DMPO) dampens lipopolysaccharide (LPS)-triggered inflammatory priming of RAW264.7 cells. Herein, we tested whether DMPO by itself can induce changes in macrophage transcriptome, and that these effects may prevent LPS-induced activation of macrophages. To test our hypothesis, we performed a transcriptomic and bioinformatics analysis in RAW264.7 cells incubated with or without LPS, in the presence or in the absence of DMPO. Functional data analysis showed 79 differentially expressed genes (DEGs) when comparing DMPO vs Control. We used DAVID databases for identifying enriched gene ontology terms and Ingenuity Pathway Analysis for functional analysis. Our data showed that DMPO vs Control comparison DEGs are related to downregulation immune-system processes among others. Functional analysis indicated that interferon-response factor 7 and toll-like receptor were related (predicted inhibitions) to the observed transcriptomic effects of DMPO. Functional data analyses of the DMPO+LPS vs LPS DEGs were consistent with DMPO dampening LPS-induced inflammatory transcriptomic profile in RAW 264.7. These changes were confirmed using Nanostring technology. Taking together our data, surprisingly, indicates that DMPO by itself affects gene expression related to regulation of immune system and that DMPO dampens LPS-triggered inflammatory transcriptomic profile. Our data provide critical data for further studies on the possible use of DMPO as a structural platform for the design of novel mechanism-based anti-inflammatory drugs.
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影响因子：
7.4
作者：
Domazou, Anastasia S.;Koppenol, Willem H.;Gebicki, Janusz M.
通讯作者：
Gebicki, Janusz M.
DOI：
10.1016/s0167-4889(98)00126-8
发表时间：
1998-11-19
影响因子：
5.1
作者：
Kotake, Y;Sang, H;Wallis, GL
通讯作者：
Wallis, GL
影响因子：
6.1
作者：
Zhai, Zili;Gomez-Mejiba, Sandra E.;Ramirez, Dario C.
通讯作者：
Ramirez, Dario C.
DOI：
10.1124/jpet.108.143479
发表时间：
2009-05-01
影响因子：
3.5
作者：
Zuo, Li;Chen, Yeong-Renn;Zweier, Jay L.
通讯作者：
Zweier, Jay L.
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