miRNA-125b regulates TNF-α production in CD14+ neonatal monocytes via post-transcriptional regulation
miRNA-125b regulates TNF-α production in CD14+ neonatal monocytes via post-transcriptional regulation
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DOI：
10.1189/jlb.1211593
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发表时间：
2012-07-01
影响因子：
5.5
通讯作者：
Yang, Kuender D.
中科院分区：
文献类型：
--
作者：
Huang, Hsin-Chun;Yu, Hong-Ren;Yang, Kuender D.
新生儿，虽然缺乏细胞免疫，经常显示败血症与增强的促炎反应。在这里，我们发现新生儿单核细胞比成人单核细胞产生更高的tnf - α mRNA和蛋白。转录因子评估发现新生儿和成人单核细胞NF-kappa B p65水平无显著差异。添加Act D来获取tnf - α mRNA的半衰期，结果显示lps诱导的tnf - α mRNA半衰期在两者之间无显著差异，而CHX显著增加了新生儿tnf - α mRNA的半衰期。这表明转录后机制涉及新生儿单核细胞tnf - α生成的增加。为了研究miRNA是否参与转录后调控，在新生儿和成年跨国公司之间进行了miRNA阵列的差异显示，同时发现了hsa-miR-103、hsa-miR-125b、hsa-miR-130a、hsa-miR-454-3p和hsa-miR-542-3p。功能验证发现，LPS刺激后，新生儿单核细胞中miR-125b的显著下降与较高的tnf - α表达相关。将miR-125b前体转染到新生儿单核细胞中，可显著抑制tnf - α mRNA和蛋白的表达，提示miR-125b负调控新生儿单核细胞中tnf - α的表达。miRNA表达的调节可能用于调节促炎反应改变的新生儿tnf - α的产生。j . Leukoc。生物学杂志。92:171-182；2012.
Neonates, although deficient in cell immunity, frequently reveal sepsis with augmented proinflammatory reactions. Here, we found that neonatal monocytes produced significantly higher TNF-alpha mRNA and protein than adult monocytes. Assessment of the transcriptional factor found no significant difference of NF-kappa B p65 level between neonatal and adult monocytes. Addition of Act D to access the half-life of TNF-alpha mRNA revealed no significant difference of the LPS-induced TNF-alpha mRNA half-life between them, whereas CHX increased neonatal TNF-alpha mRNA significantly. This suggests that a post-transcriptional mechanism involves the augmentation of TNF-alpha production by neonatal monocytes. To examine whether miRNA was involved in the post-transcriptional regulation, differential displays of miRNA array between neonatal and adult MNCs were performed, along with the discovery of hsa-miR-103, hsa-miR-125b, hsa-miR-130a, hsa-miR-454-3p, and hsa-miR-542-3p, which were greater than a twofold decrease or increase after LPS treatment for 4 h. The functional validation identified that miR-125b decreased significantly in association with higher TNF-alpha expression by neonatal monocytes after LPS stimulation. Transfection of the miR-125b precursor into neonatal monocytes significantly repressed the TNF-alpha mRNA and protein expression, suggesting that miR-125b negatively regulates TNF-alpha expression in neonatal monocytes. Modulation of miRNA expression may be used to regulate TNF-alpha production in newborns with altered proinflammatory reactions. J. Leukoc. Biol. 92: 171-182; 2012.