Open Access

Endoplasmic reticulum stress/XBP1 promotes airway mucin secretion under the influence of neutrophil elastase

  • Authors:
    • Xiaoyan Xu
    • Qi Li
    • Liang Li
    • Man Zeng
    • Xiangdong Zhou
    • Zhaozhong Cheng
  • View Affiliations

  • Published online on: March 11, 2021     https://doi.org/10.3892/ijmm.2021.4914
  • Article Number: 81
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endoplasmic reticulum (ER) stress is an important reaction of airway epithelial cells in response to various stimuli, and may also be involved in the mucin secretion process. In the present study, the effect of ER stress on neutrophil elastase (NE)‑induced mucin (MUC)5AC production in human airway epithelial cells was explored. 16HBE14o‑airway epithelial cells were cultured and pre‑treated with the reactive oxygen species (ROS) inhibitor, N‑acetylcysteine (NAC), or the ER stress chemical inhibitor, 4‑phenylbutyric acid (4‑PBA), or the cells were transfected with inositol‑requiring kinase 1α (IRE1α) small interfering RNA (siRNA) or X‑box‑binding protein 1 (XBP1) siRNA, respectively, and subsequently incubated with NE. The results obtained revealed that NE increased ROS production in the 16HBE14o‑cells, with marked increases in the levels of ER stress‑associated proteins, such as glucose‑regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phosphorylated protein kinase R‑like endoplasmic reticulum kinase (pPERK) and phosphorylated (p)IRE1α. The protein and mRNA levels of spliced XBP1 were also increased, and the level of MUC5AC protein was notably increased. The ROS scavenger NAC and ER stress inhibitor 4‑PBA were found to reduce ER stress‑associated protein expression and MUC5AC production and secretion. Further analyses revealed that MUC5AC secretion was also attenuated by IRE1α and XBP1 siRNAs, accompanied by a decreased mRNA expression of spliced XBP1. Taken together, these results demonstrate that NE induces ER stress by promoting ROS production in 16HBE14o‑airway epithelial cells, leading to increases in MUC5AC protein production and secretion via the IRE1α and XBP1 signaling pathways.
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May-2021
Volume 47 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
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Spandidos Publications style
Xu X, Li Q, Li L, Zeng M, Zhou X and Cheng Z: Endoplasmic reticulum stress/XBP1 promotes airway mucin secretion under the influence of neutrophil elastase. Int J Mol Med 47: 81, 2021
APA
Xu, X., Li, Q., Li, L., Zeng, M., Zhou, X., & Cheng, Z. (2021). Endoplasmic reticulum stress/XBP1 promotes airway mucin secretion under the influence of neutrophil elastase. International Journal of Molecular Medicine, 47, 81. https://doi.org/10.3892/ijmm.2021.4914
MLA
Xu, X., Li, Q., Li, L., Zeng, M., Zhou, X., Cheng, Z."Endoplasmic reticulum stress/XBP1 promotes airway mucin secretion under the influence of neutrophil elastase". International Journal of Molecular Medicine 47.5 (2021): 81.
Chicago
Xu, X., Li, Q., Li, L., Zeng, M., Zhou, X., Cheng, Z."Endoplasmic reticulum stress/XBP1 promotes airway mucin secretion under the influence of neutrophil elastase". International Journal of Molecular Medicine 47, no. 5 (2021): 81. https://doi.org/10.3892/ijmm.2021.4914