title: Different signal pathways regulate IL-1β-induced mature and primary miRNA-146a expression in human alveolar epithelial cells.
abstract: It was known that IL-1β-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-1β induced an increase of TRBP at 30 min, following by an extended expression at 24 h compared to the non-IL-1β 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-1β 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.
authors.affiliation: Xi'an Jiaotong University Department of Genetics and Molecular Biology, School of Medicine 76 Yanta West Road Xi'an, Shaanxi 710061 China University of Manchester NIHR Translational Research Facility in Respiratory Medicine Group, School of Translational Medicine Manchester UK.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Jiang
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D056918:Nuclear Receptor Coactivators / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D053583:Interleukin-1beta; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C486559:NCOA6 protein, human; D056918:Nuclear Receptor Coactivators; D047428:Protein Kinase Inhibitors; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: alveolar epithelial cells; inflammation; lung; miR-146a; miRNA; miRNAs biogenesis