Perry Mark M, Williams Andrew E, Tsitsiou Eleni, Larner-Svensson Hanna M, Lindsay Mark A
Airways Disease, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
FEBS Lett. 2009 Oct 20;583(20):3349-55. doi: 10.1016/j.febslet.2009.09.038. Epub 2009 Sep 26.
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-1beta-induced activation of the nuclear factor (NF)-kappaB, 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-1beta-induced miR-146a, IL-8 and RANTES production was regulated via NF-kappaB 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.
我们之前曾报道，白细胞介素（IL）-β诱导的miR-146a和miR-146b表达可负向调节人肺泡A549上皮细胞中IL-8和调节激活正常T细胞表达和分泌因子（RANTES）的释放。为了确定调节此反应的细胞内途径，我们证明了IL-1β可诱导核因子（NF）-κB、细胞外调节激酶（ERK）-1/2、c-Jun氨基末端激酶（JNK）-1/2和p38丝裂原活化蛋白（MAP）激酶途径的激活。随后的药理学研究表明，IL-1β诱导的miR-146a、IL-8和RANTES的产生是通过NF-κB和JNK-1/2调节的，而miR-146b的表达是通过MEK-1/2和JNK-1/2介导的。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。
