Formation of GW/P bodies as marker for microRNA-mediated regulation of innate immune signaling in THP-1 cells.

Formation of GW/P bodies as marker for microRNA-mediated regulation of innate immune signaling in THP-1 cells.
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DOI:
10.1038/icb.2009.84
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发表时间:
2010-02
影响因子:
4
通讯作者:
Chan, Edward K. L.
Chan, Edward K. L.
中科院分区:
医学3区
文献类型:
--
作者:
Pauley, Kaleb M.;Satoh, Minoru;Pauley, Brad A.;Dominguez-Gutierrez, Paul R.;Wallet, Shannon M.;Holliday, L. Shannon;Cha, Seunghee;Reeves, Westley H.;Chan, Edward K. L.

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GW小体(GWB或P小体)被认为是由microRNA (miRNA)调控mRNA靶点和随后的mRNA降解引起的细胞质病灶。本研究旨在探讨脂多糖(LPS)刺激人单核细胞对GW小体形成、miRNA诱导、miRNA靶点调控以及下游细胞因子和趋化因子表达的影响。在LPS刺激下,GWB数量在刺激后8小时持续增加2倍,当mirna效应蛋白Rck/p54或argonaute 2 (Ago2)耗尽时,这种增加被消除。由于在LPS刺激期间miR-146a的水平从19倍增加到100倍,因此我们检测了将miR-146a模拟物转染到THP-1细胞中,以确定单独miR-146a是否可以诱导GWB的类似变化。结果显示转染的miR-146a可以产生相当数量的GWB增加,并且伴随着LPS诱导的主要细胞因子/趋化因子的减少。这些数据表明,GWB的大小和数量的增加可能是miRNA介导的基因调控的生物标志物,miR-146a在lps诱导的THP-1细胞细胞因子产生的调控中起着重要作用。
GW bodies (GWB, or P bodies) are cytoplasmic foci thought to result from microRNA (miRNA) regulation of mRNA targets and subsequent mRNA degradation. The purpose of this study is to examine the effects of lipopolysaccharide (LPS) stimulation of human monocytes on GW body formation, miRNA induction, miRNA target regulation, and downstream cytokine and chemokine expression. In response to LPS stimulation, the number of GWB consistently increased by 2 fold at 8 hours after stimulation and this increase was abolished when the miRNA-effector proteins Rck/p54 or argonaute 2 (Ago2) were depleted. Since the level of miR-146a increased from 19 fold up to 100 fold during LPS stimulation, the transfection of a miR-146a-mimic into THP-1 cells was examined to determine whether miR-146a alone can induce similar changes in GWB. The results showed transfected miR-146a could produce a comparable increase in the number of GWB and this was accompanied by a reduction in major cytokines/chemokines induced by LPS. These data show that the increase in size and number of GWB may serve as a biomarker for miRNA mediated gene regulation, and miR-146a plays a significant role in the regulation of LPS-induced cytokine production in THP-1 cells.
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