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MiR-146a negatively regulates neutrophil elastase-induced MUC5AC secretion from 16HBE human bronchial epithelial cells

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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.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (NSFC; no.: 81070031) and China-Russia International Cooperation and Exchange Project of NSFC (no.: 81011120108).

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Authors and Affiliations

  1. Department of Respiratory Medicine, the Second Affiliated Hospital, Chongqing University of Medical Science, Chongqing, 400010, China

    Tian Zhong & Xiang-dong Zhou

  2. Far Eastern Scientific Center of Physiology and Pathology of Respiration, Russian Academy of Medical Sciences, Blagoveschensk, 675000, Russia

    Juliy M. Perelman & Victor P. Kolosov

Authors
  1. Tian Zhong
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  2. Juliy M. Perelman
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  3. Victor P. Kolosov
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  4. Xiang-dong Zhou
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Correspondence to Xiang-dong Zhou.

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Zhong, T., Perelman, J.M., Kolosov, V.P. et al. MiR-146a negatively regulates neutrophil elastase-induced MUC5AC secretion from 16HBE human bronchial epithelial cells. Mol Cell Biochem 358, 249–255 (2011). https://doi.org/10.1007/s11010-011-0975-2

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  • DOI: https://doi.org/10.1007/s11010-011-0975-2

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