Different signal pathways regulate IL-1 beta-induced mature and primary miRNA-146a expression in human alveolar epithelial cells

作者：Jiang Xiaoying^*

来源：Acta Physiologica Hungarica, 2014, 101(3): 282-290.

DOI：10.1556/APhysiol.101.2014.3.3

• lung
• inflammation
• miRNA
• miR-146a
• miRNAs biogenesis
• alveolar epithelial cells

It was known that IL-1 beta-induced rapid expression of miR-146a, which regulated the secretion of inflammatory chemokines in human A549 alveolar epithelial cells. However, little is known about the level of primary miR-146a and the downstream biogenesis of miR-146a in A549 cells. We examined the levels of primary miR-146a and mature miR-146a in A549 cells following treatment with pharmacological inhibitors of IKK-2 (TPCA-1), MEK-1/2 (PD098059), JNK-1/2 (SP600125), p38 MAPK (SB 203580) and PI-3k (LY294002). Our studies showed that exposure to PD98059, TPCA-1 and LY294002 resulted in a dose-dependent reduction in the expression of mature miR-146a while the primary miR-146a expression was not changed by any inhibitor. Western blot showed that IL-1 beta induced an increase of TRBP at 30 min, following by an extended expression at 24 h compared to the non-IL-1 beta controls in A549 cells. In conclusion, our studies indicated that miR-146a expression in alveolar epithelial cells was regulated at the post-transcriptional level via a MEK-1/2 and IKK2 pathway, and also for the first time via PI-3k pathway. The longer expression of TRBP following stimulation with IL-1 beta suggests that TRBP might play a role in the process of regulating the processing of primary miR-146a to mature miR-146a in human alveolar epithelial cells.

• 出版日期2014-9
• 单位西安交通大学