title: MiR-146a negatively regulates neutrophil elastase-induced MUC5AC secretion from 16HBE human bronchial epithelial cells.
abstract: Mucus hypersecretion is a major manifestation in patients with chronic inflammatory airway diseases, and MUC5AC protein is a major component of airway mucus. Earlier studies have demonstrated that neutrophil elastase (NE), a serine protease, mainly produced by neutrophils, stimulates the production of MUC5AC from airway epithelial cells. The microRNA miR-146a has been linked to inflammatory diseases. However, the role of miR-146a in the NE-induced MUC5AC expression remains unclear. Here, we show that NE exerts a dose- and time-dependent induction of both MUC5AC and miR-146a in human bronchial epithelial cells (16HBE). Ectopic expression of miR-146a in 16HBE cells inhibited the stimulation of MUC5AC by NE, while, conversely, depletion of endogenous miR-146a enhanced the MUC5AC production. Knockdown of intrinsic miR-146a activated both c-Jun N-terminal kinase (JNK) and nuclear factor-kappaB (NF-κB) signaling pathways. Moreover, targeting JNK or NF-κB by specific chemical inhibitors blocked the upregulation of MUC5AC by miR-146a silencing. Taken together, our data highlight a negative feedback role for miR-146a in the control of MUC5AC production from airway epithelial cells stimulated by NE, which may be associated with the inactivation of JNK and NF-κB signaling.
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital, Chongqing University of Medical Science, Chongqing 400010, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhong
authors.forename: Juliy M
authors.initials: JM
authors.lastname: Perelman
authors.forename: Victor P
authors.initials: VP
authors.lastname: Kolosov
authors.forename: Xiang-dong
authors.initials: XD
authors.lastname: Zhou
mesh_terms: D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019272:Leukocyte Elastase / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D055271:Mucin 5AC / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D055271:Mucin 5AC; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D019272:Leukocyte Elastase