Divergent intracellular pathways regulate interleukin-1β-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells
Divergent intracellular pathways regulate interleukin-1β-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells
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DOI：
10.1016/j.febslet.2009.09.038
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发表时间：
2009-10-20
期刊：
影响因子：
3.5
通讯作者：
Lindsay, Mark A.
中科院分区：
文献类型：
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作者：
Perry, Mark M.;Williams, Andrew E.;Lindsay, Mark A.
我们以前曾报道IL-β诱导的miR-146 a和miR-146 b表达负调节人肺泡A549上皮细胞中IL-8和RANTES的释放。为了确定调节这种反应的细胞内途径，我们证明了IL-1 β诱导的核因子（NF）-κ B、细胞外调节激酶（ERK）-1/2、c-jun N-末端激酶（JNK）-1/2和p38丝裂原激活激酶（MAP）激酶途径的激活。随后的药理学研究表明，IL-1b诱导的miR-146 a、IL-8和RANTES的产生通过NF-κ B和JNK-1/2调节，而miR-146 B的表达通过MEK-1/2和JNK-1/2介导。这些不同的细胞内途径可能解释了miR-146亚型的差异表达和生物学作用。皇冠版权所有（C）2009由Elsevier B出版。五、代表欧洲生物化学学会联合会。All rights reserved.
We have previously reported that IL-beta-induced miR-146a and miR-146b expression negatively regulates IL-8 and RANTES release in human alveolar A549 epithelial cells. To determine the intracellular pathways that regulate this response, we demonstrate IL-1 beta-induced activation of the nuclear factor (NF)-kappa B, extracellular regulated kinase (ERK)-1/2, c-jun N-terminal kinase (JNK)-1/2 and p38 mitogen activated kinase (MAP) kinase pathways. Subsequent pharmacological studies show that IL-1b-induced miR-146a, IL-8 and RANTES production was regulated via NF-kappa B and JNK-1/2 whilst miR-146b expression was mediated via MEK-1/2 and JNK-1/2. These divergent intracellular pathways likely explain the differential expression and biological action of the miR-146 isoforms. Crown Copyright (C) 2009 Published by Elsevier B. V. on behalf of Federation of European Biochemical society. All rights reserved.