MicroRNA-125b modulates inflammatory chemokine CCL4 expression in immune cells and its reduction causes CCL4 increase with age.
MicroRNA-125b modulates inflammatory chemokine CCL4 expression in immune cells and its reduction causes CCL4 increase with age.
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DOI：
10.1111/acel.12294
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发表时间：
2015-04
期刊：
影响因子：
7.8
通讯作者：
Weng NP
中科院分区：
文献类型：
--
作者：
Cheng NL;Chen X;Kim J;Shi AH;Nguyen C;Wersto R;Weng NP
趋化因子通过严格控制的表达在调节免疫应答中起关键作用。炎症趋化因子水平的升高通常随着年龄的增长而发生，但这种与年龄相关的变化的机制尚未完全了解。在这里，我们报告了microRNA-125 b（miR-125 b）在调节人类免疫细胞中炎症性CC趋化因子4（CCL 4）表达中的作用及其随衰老而改变的表达。我们首先分析了年轻（≤42岁）和老年（≥70岁）成人血液中8种不同类型免疫细胞中CCL 4的mRNA水平，包括CD 4和CD 8 T细胞亚群（幼稚、中枢和效应记忆）、B细胞和单核细胞。我们观察到单核细胞和幼稚CD 8 T细胞表达更高水平的CCL 4，并表现出与年龄相关的CCL 4增加。然后，我们发现miR-125 b的水平与这些细胞中CCL 4的水平呈负相关，与年轻人相比，老年人的单核细胞和幼稚CD 8 T细胞中miR-125 b的水平降低。在单核细胞和幼稚CD 8 T细胞中通过shRNA敲低miR-125 b导致CCL 4蛋白增加，而在幼稚CD 8 T细胞中通过转染增强miR-125 b表达导致CCL 4 mRNA和蛋白对刺激的响应减少。最后，我们证明了miR-125 b的作用需要CCL 4 3′UTR中的“种子”序列。总之，这些发现表明miR-125 b是CCL 4的负调控因子，其减少部分负责CCL 4的年龄相关性增加。
Chemokines play a pivotal role in regulating the immune response through a tightly controlled expression. Elevated levels of inflammatory chemokines commonly occur with aging but the mechanism underlying this age-associated change is not fully understood. Here, we report the role of microRNA-125b (miR-125b) in regulating inflammatory CC chemokine 4 (CCL4) expression in human immune cells and its altered expression with aging. We first analyzed the mRNA level of CCL4 in eight different types of immune cells including CD4 and CD8 T-cell subsets (naïve, central and effector memory), B cells and monocytes in blood from both young (≤42 years) and old (≥70 years) adults. We observed that monocytes and naïve CD8 T cells expressed higher levels of CCL4 and exhibited an age-related increase in CCL4. We then found the level of miR-125b was inversely correlated with the level of CCL4 in these cells, and the level of miR-125b was reduced in monocytes and naïve CD8 T cells of the old compared to the young adults. Knock-down of miR-125b by shRNA in monocytes and naïve CD8 T cells led to an increase of CCL4 protein, whereas enhanced miR-125b expression by transfection in naïve CD8 T cells resulted in a reduction of the CCL4 mRNA and protein in response to stimulation. Finally, we demonstrated that miR-125b action requires the ‘seed’ sequence in 3′UTR of CCL4. Together these findings demonstrated that miR-125b is a negative regulator of CCL4 and its reduction is partially responsible for the age-related increase of CCL4.
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影响因子：
10.5
作者：
Salama R;Sadaie M;Hoare M;Narita M
通讯作者：
Narita M
影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
DOI：
10.1073/pnas.1016218107
发表时间：
2010-12-14
影响因子：
11.1
作者：
Ooi, A. G. Lisa;Sahoo, Debashis;Park, Christopher Y.
通讯作者：
Park, Christopher Y.
DOI：
10.1016/j.biocel.2003.10.019
发表时间：
2004-10-01
影响因子：
4
作者：
Maurer, M;von Stebut, E
通讯作者：
von Stebut, E
影响因子：
64.8
作者：
Sallusto, F;Lenig, D;Lanzavecchia, A
通讯作者：
Lanzavecchia, A