Dexamethasone attenuates methacholine-mediated aquaporin 5 downregulation in human nasal epithelial cells via suppression of NF-κB activation

Yung Lung Chang, Kai Ren Jian, Chun Shu Lin, Hsing Won Wang, Shao Cheng Liu

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2 Citations (Scopus)

Abstract

Background: Cholinergic stimulation plays a major role in inflammatory airway diseases. However, its role in airway surface liquid homeostasis and aquaporin 5 (AQP5) regulation remains unclear. In this study we sought to determine the effects of methacholine and dexamethasone on AQP5 expression in human nasal epithelial cells (HNEpC). Methods: HNEpC were cultured with methacholine or dexamethasone at 4 concentrations in vitro. The subcellular distribution of AQP5 was explored using immunocytochemistry. The pharmacologic effects of methacholine and dexamethasone on the expression of the phosphorylation of cyclic adenosine monophosphate-responsive element binding protein (p-CREB), AQP5, and nuclear factor-kappaB (NF-κB) were examined using Western blotting. Results: AQP5 was found to be located in cell membrane and cytoplasm and present in every group without a statistically significant difference. Methacholine inhibited expression of AQP5 and p-CREB in HNEpC, whereas dexamethasone increased these protein levels dose-dependently in a statistically significant manner. In turn, HNEpC treated with methacholine and dexamethasone showed the same trends as those intervened separately with these 2 drugs. Moreover, dexamethasone had the ability to reverse the inhibitory effect of methacholine. Western blotting revealed that, after incubation with 10-4 mol/L methacholine, NF-κB increased significantly, by 186.67%, compared with the untreated control group. Again, such an increase could be significantly reversed after dexamethasone treatment. Conclusion: NF-κB activation is important for inhibition of p-CREB/AQP5 expression after methacholine intervention, and dexamethasone adjusts it to the opposite side. This observation could provide additional insight into the anti-inflammatory effects of glucocorticoids that contribute to maintaining airway surface liquid and mucosal defense.

Original languageEnglish
JournalInternational Forum of Allergy and Rhinology
DOIs
Publication statusAccepted/In press - 2017
Externally publishedYes

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Keywords

  • AQP5
  • CREB
  • Dexamethasone
  • Methacholine
  • Nasal mucosa
  • NF-κB

ASJC Scopus subject areas

  • Immunology and Allergy
  • Otorhinolaryngology

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